USNCTAM perspectives on mechanics in medicine

Over decades, the theoretical and applied mechanics community has developed sophisticated approaches for analysing the behaviour of complex engineering systems. Most of these approaches have targeted systems in the transportation, materials, defence and energy industries. Applying and further developing engineering approaches for understanding, predicting and modulating the response of complicated biomedical processes not only holds great promise in meeting societal needs, but also poses serious challenges. This report, prepared for the US National Committee on Theoretical and Applied Mechanics, aims to identify the most pressing challenges in biological sciences and medicine that can be tackled within the broad field of mechanics. This echoes and complements a number of national and international initiatives aiming at fostering interdisciplinary biomedical research. This report also comments on cultural/educational challenges. Specifically, this report focuses on three major thrusts in which we believe mechanics has and will continue to have a substantial impact. (i) Rationally engineering injectable nano/microdevices for imaging and therapy of disease. Within this context, we discuss nanoparticle carrier design, vascular transport and adhesion, endocytosis and tumour growth in response to therapy, as well as uncertainty quantification techniques to better connect models and experiments. (ii) Design of biomedical devices, including point-of-care diagnostic systems, model organ and multi-organ microdevices, and pulsatile ventricular assistant devices. (iii) Mechanics of cellular processes, including mechanosensing and mechanotransduction, improved characterization of cellular constitutive behaviour, and microfluidic systems for single-cell studies.

[1]  Akif Ündar,et al.  Mechanical Circulatory Support for End-Stage Heart Failure in Repaired and Palliated Congenital Heart Disease , 2011, Current cardiology reviews.

[2]  D. Mozaffarian,et al.  Heart disease and stroke statistics--2010 update: a report from the American Heart Association. , 2010, Circulation.

[3]  Juan G Santiago,et al.  Detection of 100 aM fluorophores using a high-sensitivity on-chip CE system and transient isotachophoresis. , 2007, Analytical chemistry.

[4]  Daniel A. Fletcher,et al.  Cell mechanics and the cytoskeleton , 2010, Nature.

[5]  Minutes,et al.  MOLECULAR IMAGING IN DRUG DISCOVERY AND DEVELOPMENT , 2003 .

[6]  Bo Huang,et al.  Counting Low-Copy Number Proteins in a Single Cell , 2007, Science.

[7]  R K Jain,et al.  Vascular permeability in a human tumour xenograft: molecular charge dependence , 2000, British Journal of Cancer.

[8]  D. Ingber,et al.  Reconstituting Organ-Level Lung Functions on a Chip , 2010, Science.

[9]  Shuming Nie,et al.  Understanding and overcoming major barriers in cancer nanomedicine. , 2010, Nanomedicine.

[10]  Huajian Gao,et al.  A universal law for cell uptake of one-dimensional nanomaterials. , 2014, Nano letters.

[11]  F. Dosio,et al.  Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential , 2006, International journal of nanomedicine.

[12]  Cass T. Miller,et al.  A multiphase model for three-dimensional tumor growth , 2013, New journal of physics.

[13]  J. Gong,et al.  Label-free attomolar detection of proteins using integrated nanoelectronic and electrokinetic devices. , 2010, Small.

[14]  Arezou A Ghazani,et al.  Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. , 2006, Nano letters.

[15]  Mauro Ferrari,et al.  Design maps for nanoparticles targeting the diseased microvasculature. , 2008, Biomaterials.

[16]  Wing Kam Liu,et al.  Immersed finite element method for rigid body motions in the incompressible Navier–Stokes flow , 2008 .

[17]  Mauro Ferrari,et al.  Nanotechnology for breast cancer therapy , 2009, Biomedical microdevices.

[18]  Edward Chu,et al.  A history of cancer chemotherapy. , 2008, Cancer research.

[19]  N A Peppas,et al.  New challenges in biomaterials. , 1994, Science.

[20]  Alex H de Vries,et al.  A coarse-grained model for polyethylene oxide and polyethylene glycol: conformation and hydrodynamics. , 2009, The journal of physical chemistry. B.

[21]  Kristoffer G. van der Zee,et al.  Numerical simulation of a thermodynamically consistent four‐species tumor growth model , 2012, International journal for numerical methods in biomedical engineering.

[22]  Marc Dellian,et al.  Neovascular targeting therapy: paclitaxel encapsulated in cationic liposomes improves antitumoral efficacy. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[23]  Lucy T. Zhang,et al.  Immersed finite element method , 2004 .

[24]  Ying Li Endocytosis of PEGylated nanoparticles: what is the role of grafted polyethylene glycol? , 2014 .

[25]  Vladimir P Torchilin,et al.  Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors. , 2002, Cancer research.

[26]  R. Jain,et al.  Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft. , 1994, Cancer research.

[27]  Dong-Pyo Kim,et al.  Droplet electroporation in microfluidics for efficient cell transformation with or without cell wall removal. , 2012, Lab on a chip.

[28]  Jinming Gao,et al.  Modeling particle shape-dependent dynamics in nanomedicine. , 2011, Journal of nanoscience and nanotechnology.

[29]  Xiaogang Qu,et al.  Carboxyl-modified single-walled carbon nanotubes selectively induce human telomeric i-motif formation , 2006, Proceedings of the National Academy of Sciences.

[30]  Dean Ho,et al.  Synthesis of nanodiamond-daunorubicin conjugates to overcome multidrug chemoresistance in leukemia. , 2014, Nanomedicine : nanotechnology, biology, and medicine.

[31]  Xiangrong Li,et al.  Nonlinear simulations of solid tumor growth using a mixture model: invasion and branching , 2009, Journal of mathematical biology.

[32]  Ted Belytschko,et al.  Immersed electrokinetic finite element method , 2007 .

[33]  David G Spiller,et al.  Quantitative measurement of single cell dynamics. , 2012, Current opinion in biotechnology.

[34]  Tim Liedl,et al.  Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. , 2005, Nano letters.

[35]  Mauro Ferrari,et al.  Design of bio-mimetic particles with enhanced vascular interaction. , 2009, Journal of biomechanics.

[36]  I Usa,et al.  Coarse grained molecular dynamics and theoretical studies of carbon nanotubes entering cell membrane , 2008 .

[37]  George C Schatz,et al.  Atomistic simulation and measurement of pH dependent cancer therapeutic interactions with nanodiamond carrier. , 2011, Molecular pharmaceutics.

[38]  Lani F. Wu,et al.  Cellular Heterogeneity: Do Differences Make a Difference? , 2010, Cell.

[39]  Samir Mitragotri,et al.  Particle shape: a new design parameter for micro- and nanoscale drug delivery carriers. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[40]  Jaehong Key,et al.  Engineering discoidal polymeric nanoconstructs with enhanced magneto-optical properties for tumor imaging. , 2013, Biomaterials.

[41]  Robert Langer,et al.  Endothelialized microvasculature based on a biodegradable elastomer. , 2005, Tissue engineering.

[42]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[43]  Mathias Brust,et al.  Uptake and intracellular fate of surface-modified gold nanoparticles. , 2008, ACS nano.

[44]  Haiping Fang,et al.  Destructive extraction of phospholipids from Escherichia coli membranes by graphene nanosheets. , 2013, Nature nanotechnology.

[45]  Ying Li,et al.  Multiscale modeling and uncertainty quantification in nanoparticle-mediated drug/gene delivery , 2014 .

[46]  Hongyu Zhou,et al.  A nano-combinatorial library strategy for the discovery of nanotubes with reduced protein-binding, cytotoxicity, and immune response. , 2008, Nano letters.

[47]  Hyun-Boo Lee,et al.  Electrolyte-free Amperometric Immunosensor using a Dendritic Nanotip. , 2013, RSC advances.

[48]  M Ferrari,et al.  The role of specific and non-specific interactions in receptor-mediated endocytosis of nanoparticles. , 2007, Biomaterials.

[49]  Huajian Gao,et al.  Size and shape effects on diffusion and absorption of colloidal particles near a partially absorbing sphere: implications for uptake of nanoparticles in animal cells. , 2008, Physical review. E, Statistical, nonlinear, and soft matter physics.

[50]  Sanjiv S Gambhir,et al.  Family of enhanced photoacoustic imaging agents for high-sensitivity and multiplexing studies in living mice. , 2012, ACS nano.

[51]  Mandy B. Esch,et al.  Microfabricated mammalian organ systems and their integration into models of whole animals and humans. , 2013, Lab on a chip.

[52]  Francesco Stellacci,et al.  Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles. , 2008, Nature materials.

[53]  Younan Xia,et al.  The effects of size, shape, and surface functional group of gold nanostructures on their adsorption and internalization by cells. , 2010, Small.

[54]  W. Yeo,et al.  Rapid extraction and preservation of genomic DNA from human samples , 2013, Analytical and Bioanalytical Chemistry.

[55]  Oliver Gaemperli,et al.  Non-invasive anatomic and functional imaging of vascular inflammation and unstable plaque. , 2012, European heart journal.

[56]  R. Bashir,et al.  Creating Living Cellular Machines , 2013, Annals of Biomedical Engineering.

[57]  L. Hood,et al.  Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood , 2008, Nature Biotechnology.

[58]  R. A. Uras,et al.  Generalized multiple scale reproducing kernel particle methods , 1996 .

[59]  D. Discher,et al.  Shape effects of filaments versus spherical particles in flow and drug delivery. , 2007, Nature nanotechnology.

[60]  Ji Guo,et al.  Nanofabricated particles for engineered drug therapies: a preliminary biodistribution study of PRINT nanoparticles. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[61]  S. Franzen,et al.  Multifunctional gold nanoparticle-peptide complexes for nuclear targeting. , 2003, Journal of the American Chemical Society.

[62]  Woon-Hong Yeo,et al.  Dielectrophoretic concentration of low-abundance nanoparticles using a nanostructured tip , 2012, Nanotechnology.

[63]  Kai Yang,et al.  Computer simulation of the translocation of nanoparticles with different shapes across a lipid bilayer. , 2010, Nature nanotechnology.

[64]  Bo Yu,et al.  Nanochannel electroporation delivers precise amounts of biomolecules into living cells. , 2011, Nature nanotechnology.

[65]  M Ferrari,et al.  The receptor-mediated endocytosis of nonspherical particles. , 2008, Biophysical journal.

[66]  Chang Lu,et al.  One-step extraction of subcellular proteins from eukaryotic cells. , 2010, Lab on a chip.

[67]  Paolo Decuzzi,et al.  Vascular deposition patterns for nanoparticles in an inflamed patient-specific arterial tree , 2014, Biomechanics and modeling in mechanobiology.

[68]  Huajian Gao,et al.  Cellular uptake of elastic nanoparticles. , 2011, Physical review letters.

[69]  Mauro Ferrari,et al.  Rapid tumoritropic accumulation of systemically injected plateloid particles and their biodistribution. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[70]  Juan B. Blanco-Canosa,et al.  Cellular uptake and fate of PEGylated gold nanoparticles is dependent on both cell-penetration peptides and particle size. , 2011, ACS nano.

[71]  Ben Fabry,et al.  Cell and tissue mechanics in cell migration. , 2013, Experimental cell research.

[72]  Huajian Gao,et al.  Probing mechanical principles of focal contacts in cell–matrix adhesion with a coupled stochastic–elastic modelling framework , 2011, Journal of The Royal Society Interface.

[73]  M Ferrari,et al.  The adhesive strength of non-spherical particles mediated by specific interactions. , 2006, Biomaterials.

[74]  Malisa Sarntinoranont,et al.  Interstitial Stress and Fluid Pressure Within a Growing Tumor , 2004, Annals of Biomedical Engineering.

[75]  Lucy T. Zhang,et al.  Coupling of Navier–Stokes equations with protein molecular dynamics and its application to hemodynamics , 2004 .

[76]  Ying Li,et al.  Primitive chain network study on uncrosslinked and crosslinked cis-polyisoprene polymers , 2011 .

[77]  M. Steven Greene,et al.  Quantifying uncertainties in the microvascular transport of nanoparticles , 2014, Biomechanics and modeling in mechanobiology.

[78]  Brandon J. Tefft,et al.  Enhancing Endothelial Cell Retention on ePTFE Constructs by siRNA-Mediated SHP-1 Gene , 2011 .

[79]  Ying Li,et al.  Challenges in Multiscale Modeling of Polymer Dynamics , 2013 .

[80]  Douglas A. Lauffenburger,et al.  Polyfunctional responses by human T cells result from sequential release of cytokines , 2011, Proceedings of the National Academy of Sciences.

[81]  Huajian Gao,et al.  Lifetime and strength of periodic bond clusters between elastic media under inclined loading. , 2009, Biophysical journal.

[82]  Ying Li,et al.  The archetype-genome exemplar in molecular dynamics and continuum mechanics , 2014 .

[83]  Chang Lu,et al.  Release of intracellular proteins by electroporation with preserved cell viability. , 2012, Analytical chemistry.

[84]  Shuming Nie,et al.  Nanotechnology for targeted cancer therapy , 2007, Expert review of anticancer therapy.

[85]  Mauro Ferrari,et al.  Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. , 2008, Nature nanotechnology.

[86]  Mauro Ferrari,et al.  Three phase flow dynamics in tumor growth , 2014 .

[87]  Wing Kam Liu,et al.  The immersed/fictitious element method for fluid–structure interaction: Volumetric consistency, compressibility and thin members , 2008 .

[88]  Vicki Stone,et al.  An in vitro study of the potential of carbon nanotubes and nanofibres to induce inflammatory mediators and frustrated phagocytosis , 2007 .

[89]  Cass T. Miller,et al.  Thermodynamically constrained averaging theory approach for modeling flow and transport phenomena in porous medium systems: 1. Motivation and overview , 2005 .

[90]  Thomas J. R. Hughes,et al.  Patient-Specific Vascular NURBS Modeling for Isogeometric Analysis of Blood Flow , 2007, IMR.

[91]  Woon-Hong Yeo,et al.  Nanoscale sensor analysis using the immersed molecular electrokinetic finite element method. , 2012, Nanoscale.

[92]  Subra Suresh,et al.  Size‐Dependent Endocytosis of Nanoparticles , 2009, Advanced materials.

[93]  Wing Kam Liu,et al.  Mathematical foundations of the immersed finite element method , 2006 .

[94]  Wei Liu,et al.  Protein Binding by Functionalized Multiwalled Carbon Nanotubes Is Governed by the Surface Chemistry of Both Parties and the Nanotube Diameter , 2008 .

[95]  Ying Li,et al.  A predictive multiscale computational framework for viscoelastic properties of linear polymers , 2012 .

[96]  U. Heinzmann,et al.  Residence Time in Niches of Stagnant Flow Determines Fibrin Clot Formation in an Arterial Branching Model - Detailed Flow Analysis and Experimental Results , 1995, Thrombosis and Haemostasis.

[97]  Wing Kam Liu,et al.  Reproducing kernel particle methods for structural dynamics , 1995 .

[98]  Martin Kröger,et al.  Endocytosis of PEGylated nanoparticles accompanied by structural and free energy changes of the grafted polyethylene glycol. , 2014, Biomaterials.

[99]  Salvatore Torquato,et al.  Motivation and Overview , 2002 .

[100]  Dino Di Carlo,et al.  Dynamic single-cell analysis for quantitative biology. , 2006, Analytical chemistry.

[101]  Biswajit Saha,et al.  Multiscale Simulation as a Framework for the Enhanced Design of Nanodiamond-Polyethylenimine-based Gene Delivery. , 2012, The journal of physical chemistry letters.

[102]  Mauro Ferrari,et al.  Intravascular Delivery of Particulate Systems: Does Geometry Really Matter? , 2008, Pharmaceutical Research.

[103]  Ying Zheng,et al.  In vitro microvessels for the study of angiogenesis and thrombosis , 2012, Proceedings of the National Academy of Sciences.

[104]  Wing Kam Liu,et al.  Multiple‐scale reproducing kernel particle methods for large deformation problems , 1998 .

[105]  Lucy T. Zhang,et al.  On computational issues of immersed finite element methods , 2009, J. Comput. Phys..

[106]  B. Snijder,et al.  Origins of regulated cell-to-cell variability , 2011, Nature Reviews Molecular Cell Biology.

[107]  David A. Rand,et al.  Measurement of single-cell dynamics , 2010, Nature.

[108]  Stephen R Quake,et al.  Whole-genome molecular haplotyping of single cells , 2011, Nature Biotechnology.

[109]  Samir Mitragotri,et al.  Control of endothelial targeting and intracellular delivery of therapeutic enzymes by modulating the size and shape of ICAM-1-targeted carriers. , 2008, Molecular therapy : the journal of the American Society of Gene Therapy.

[110]  Woon-Hong Yeo,et al.  Size-selective immunofluorescence of Mycobacterium tuberculosis cells by capillary- and viscous forces. , 2010, Lab on a chip.

[111]  Wing Kam Liu,et al.  Dielectrophoretic assembly of nanowires. , 2006, The journal of physical chemistry. B.

[112]  Daniel A. Heller,et al.  Treating metastatic cancer with nanotechnology , 2011, Nature Reviews Cancer.

[113]  Hyunjae Lee,et al.  Engineering of functional, perfusable 3D microvascular networks on a chip. , 2013, Lab on a chip.

[114]  M. Ferrari,et al.  A Theoretical Model for the Margination of Particles within Blood Vessels , 2005, Annals of Biomedical Engineering.

[115]  Huajian Gao,et al.  Lifetime and strength of adhesive molecular bond clusters between elastic media. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[116]  Giuseppe Pascazio,et al.  The preferential targeting of the diseased microvasculature by disk-like particles. , 2012, Biomaterials.

[117]  Huixin He,et al.  DNA and carbon nanotubes as medicine. , 2010, Advanced drug delivery reviews.

[118]  Mauro Ferrari,et al.  Tailoring the degradation kinetics of mesoporous silicon structures through PEGylation. , 2010, Journal of biomedical materials research. Part A.

[119]  Chad A Mirkin,et al.  A bio-barcode assay for on-chip attomolar-sensitivity protein detection. , 2006, Lab on a chip.

[120]  J. Karp,et al.  Nanocarriers as an Emerging Platform for Cancer Therapy , 2022 .

[121]  Dimitris Tousoulis,et al.  Vulnerable plaque and inflammation: potential clinical strategies. , 2011, Current pharmaceutical design.

[122]  S. Jun,et al.  Multiresolution reproducing kernel particle methods , 1997 .

[123]  S. Mitragotri,et al.  Making polymeric micro- and nanoparticles of complex shapes , 2007, Proceedings of the National Academy of Sciences.

[124]  Joseph M DeSimone,et al.  Direct fabrication and harvesting of monodisperse, shape-specific nanobiomaterials. , 2005, Journal of the American Chemical Society.

[125]  Joseph M. DeSimone,et al.  Using mechanobiological mimicry of red blood cells to extend circulation times of hydrogel microparticles , 2011, Proceedings of the National Academy of Sciences.

[126]  Huajian Gao,et al.  Graphene microsheets enter cells through spontaneous membrane penetration at edge asperities and corner sites , 2013, Proceedings of the National Academy of Sciences.

[127]  Masayuki Ito,et al.  ‘Living’ PEGylation on gold nanoparticles to optimize cancer cell uptake by controlling targeting ligand and charge densities , 2013, Nanotechnology.

[128]  Ou Chen,et al.  Fluorescent nanorods and nanospheres for real-time in vivo probing of nanoparticle shape-dependent tumor penetration. , 2011, Angewandte Chemie.

[129]  A. J. Booker,et al.  A rigorous framework for optimization of expensive functions by surrogates , 1998 .

[130]  Warren C W Chan,et al.  Mediating tumor targeting efficiency of nanoparticles through design. , 2009, Nano letters.

[131]  Yaling Liu,et al.  Rheology of red blood cell aggregation by computer simulation , 2006, J. Comput. Phys..

[132]  S. Lindström,et al.  Miniaturization of biological assays -- overview on microwell devices for single-cell analyses. , 2011, Biochimica et biophysica acta.

[133]  S. Nie,et al.  A reexamination of active and passive tumor targeting by using rod-shaped gold nanocrystals and covalently conjugated peptide ligands. , 2010, ACS nano.

[134]  H. Frieboes,et al.  Nonlinear modelling of cancer: bridging the gap between cells and tumours , 2010, Nonlinearity.

[135]  M Ferrari,et al.  The effect of shape on the margination dynamics of non-neutrally buoyant particles in two-dimensional shear flows. , 2008, Journal of biomechanics.

[136]  Albert van den Berg,et al.  Single cells or large populations? , 2007, Lab on a chip.

[137]  Craig A. Poland,et al.  Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma , 2010, Particle and Fibre Toxicology.

[138]  P. Alivisatos The use of nanocrystals in biological detection , 2004, Nature Biotechnology.

[139]  Mauro Ferrari,et al.  On Computational Modeling in Tumor Growth , 2013, Archives of Computational Methods in Engineering.

[140]  Wing Kam Liu,et al.  Reproducing kernel particle methods , 1995 .

[141]  L Preziosi,et al.  An elasto-visco-plastic model of cell aggregates. , 2010, Journal of theoretical biology.

[142]  Huajian Gao,et al.  Soft Matrices Suppress Cooperative Behaviors among Receptor-Ligand Bonds in Cell Adhesion , 2010, PloS one.

[143]  Wing Kam Liu,et al.  Extended immersed boundary method using FEM and RKPM , 2004 .

[144]  Warren C W Chan,et al.  The effect of nanoparticle size, shape, and surface chemistry on biological systems. , 2012, Annual review of biomedical engineering.

[145]  Yoon-Suk Chang,et al.  Numerical simulation of a nanoparticle focusing lens in a microfluidic channel by using immersed finite element method. , 2009, Journal of nanoscience and nanotechnology.

[146]  Yuri Bazilevs,et al.  Shape optimization of pulsatile ventricular assist devices using FSI to minimize thrombotic risk , 2014 .

[147]  Samir Mitragotri,et al.  Role of target geometry in phagocytosis. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[148]  John Quackenbush,et al.  Why Is There a Lack of Consensus on Molecular Subgroups of Glioblastoma? Understanding the Nature of Biological and Statistical Variability in Glioblastoma Expression Data , 2011, PloS one.

[149]  M Ferrari,et al.  Size and shape effects in the biodistribution of intravascularly injected particles. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[150]  Paolo Decuzzi,et al.  On the near-wall accumulation of injectable particles in the microcirculation: smaller is not better , 2013, Scientific Reports.

[151]  A. L. Marsden,et al.  Computation of residence time in the simulation of pulsatile ventricular assist devices , 2014 .

[152]  David Farrell,et al.  Immersed finite element method and its applications to biological systems. , 2006, Computer methods in applied mechanics and engineering.

[153]  Majlinda Lako,et al.  Editorial: Our Top 10 Developments in Stem Cell Biology over the Last 30 Years , 2012, Stem cells.

[154]  Tejal A Desai,et al.  Micromachined devices: the impact of controlled geometry from cell-targeting to bioavailability. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[155]  Majid Minary-Jolandan,et al.  Nanofountain probe electroporation (NFP-E) of single cells. , 2013, Nano letters.

[156]  M. Ferrari Cancer nanotechnology: opportunities and challenges , 2005, Nature Reviews Cancer.

[157]  M. Ferrari,et al.  What does physics have to do with cancer? , 2011, Nature Reviews Cancer.

[158]  Heinz-Peter Schlemmer,et al.  PET/MRI: Paving the Way for the Next Generation of Clinical Multimodality Imaging Applications , 2010, Journal of Nuclear Medicine.

[159]  Arezou A Ghazani,et al.  Assessing the effect of surface chemistry on gold nanorod uptake, toxicity, and gene expression in mammalian cells. , 2008, Small.

[160]  Y. Fung,et al.  Biomechanics: Mechanical Properties of Living Tissues , 1981 .

[161]  Adrian M. Kopacz,et al.  Immersed molecular electrokinetic finite element method , 2013 .

[162]  Jesús A. Izaguirre,et al.  COMPUCELL, a multi-model framework for simulation of morphogenesis , 2004, Bioinform..

[163]  Huajian Gao,et al.  Mechanics of receptor-mediated endocytosis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[164]  R. Jain,et al.  Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[165]  Vladimir P Torchilin,et al.  Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo , 2005, Nature Medicine.

[166]  Mauro Ferrari,et al.  Frontiers in cancer nanomedicine: directing mass transport through biological barriers. , 2010, Trends in biotechnology.

[167]  Huajian Gao,et al.  Surface-structure-regulated penetration of nanoparticles across a cell membrane. , 2012, Nanoscale.

[168]  Lucy T. Zhang,et al.  Stent modeling using immersed finite element method , 2006 .

[169]  R. Weissleder,et al.  Molecular imaging in drug discovery and development , 2003, Nature Reviews Drug Discovery.

[170]  Huajian Gao,et al.  Cell entry of one-dimensional nanomaterials occurs by tip recognition and rotation. , 2011, Nature nanotechnology.

[171]  Lance L. Munn,et al.  Fluid forces control endothelial sprouting , 2011, Proceedings of the National Academy of Sciences.

[172]  Mauro Ferrari,et al.  Problems in (nano)medical mechanics , 2013 .

[173]  D. Mozaffarian,et al.  Executive summary: heart disease and stroke statistics--2010 update: a report from the American Heart Association. , 2010, Circulation.

[174]  Adrian M. Kopacz,et al.  Design and Optimization of a Nanotip Sensor via Immersed Molecular Electrokinetic Finite Element Method , 2010 .

[175]  Michael J. Thrall,et al.  Human Lung Cancer Cells Grown in an Ex Vivo 3D Lung Model Produce Matrix Metalloproteinases Not Produced in 2D Culture , 2012, PloS one.

[176]  Roger D. Kamm,et al.  Microfluidic Platforms for Studies of Angiogenesis, Cell Migration, and Cell–Cell Interactions , 2010, Annals of Biomedical Engineering.

[177]  R. Ross,et al.  Atherosclerosis is an inflammatory disease. , 1998, American heart journal.

[178]  Woon-Hong Yeo,et al.  Nanotip analysis for dielectrophoretic concentration of nanosized viral particles , 2013, Nanotechnology.

[179]  Yu-Hsiang Hsu,et al.  In vitro perfused human capillary networks. , 2013, Tissue engineering. Part C, Methods.

[180]  R. Jain,et al.  Delivering nanomedicine to solid tumors , 2010, Nature Reviews Clinical Oncology.

[181]  Stephanie E. A. Gratton,et al.  The effect of particle design on cellular internalization pathways , 2008, Proceedings of the National Academy of Sciences.

[182]  Mauro Ferrari,et al.  In silico vascular modeling for personalized nanoparticle delivery. , 2013, Nanomedicine.

[183]  Yuri Bazilevs,et al.  Computational Fluid-Structure Interaction: Methods and Applications , 2013 .

[184]  Sei-Young Lee,et al.  Shaping nano-/micro-particles for enhanced vascular interaction in laminar flows , 2009, Nanotechnology.

[185]  Samir Mitragotri,et al.  Polymer particle shape independently influences binding and internalization by macrophages. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[186]  G. Whitesides,et al.  Patterning proteins and cells using soft lithography. , 1999, Biomaterials.

[187]  Adrian M. Kopacz,et al.  Simulation and prediction of endothelial cell adhesion modulated by molecular engineering , 2008 .

[188]  Cheng Ling Chang,et al.  Manipulation of nanoparticles and biomolecules by electric field and surface tension , 2008 .

[189]  I. Szleifer,et al.  Confinement induced lateral segregation of polymer coated nanospheres , 2012 .

[190]  Neelesh A. Patankar,et al.  The immersed molecular finite element method , 2012 .

[191]  Agnes B Kane,et al.  Biopersistence and potential adverse health impacts of fibrous nanomaterials: what have we learned from asbestos? , 2009, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[192]  S. Wise Nanocarriers as an emerging platform for cancer therapy , 2007 .

[193]  Victor M. Calo,et al.  Mathematical modeling of coupled drug and drug-encapsulated nanoparticle transport in patient-specific coronary artery walls , 2012 .

[194]  Yuri Bazilevs,et al.  Fluid–structure interaction simulation of pulsatile ventricular assist devices , 2013, Computational Mechanics.

[195]  Matthew H. M. Lim,et al.  Perfused multiwell plate for 3D liver tissue engineering. , 2010, Lab on a chip.

[196]  Maurizio Prato,et al.  Cationic carbon nanotubes bind to CpG oligodeoxynucleotides and enhance their immunostimulatory properties. , 2005, Journal of the American Chemical Society.