Visualizing Intercellular Tensile Forces by DNA-Based Membrane Molecular Probes.

Mechanical forces play critical roles in collective cell behaviors such as cell migration, proliferation, and differentiation. Extensive efforts have been made to measure forces between cells and extracellular matrices. However, force studies at cell-cell junctions remain a challenge. Herein, we reported a novel strategy to construct membrane DNA tension probes to visualize tensile forces at cell junctions. These lipid-modified probes can self-assemble onto cell membranes with high efficiency and stability. Upon experiencing tensile forces generated by neighboring cells, unfolding of the probes leads to a large increase in the fluorescence intensity. Compatible with readily accessible fluorescence microscopes, these easy-to-use membrane DNA tension probes can be broadly used to measure intercellular tensile forces.

[1]  E Bell,et al.  Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[2]  M. Eisenstein.  Mechanobiology: A measure of molecular muscle , 2017, Nature.

[3]  D E Leckband,et al.  Cadherin adhesion and mechanotransduction. , 2014, Annual review of cell and developmental biology.

[4]  W. Zimmermann,et al.  Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes. , 2000, Biotechnology and bioengineering.

[5]  Wesley R. Legant,et al.  Multidimensional traction force microscopy reveals out-of-plane rotational moments about focal adhesions , 2012, Proceedings of the National Academy of Sciences.

[6]  Weihong Tan,et al.  DNA probes for monitoring dynamic and transient molecular encounters on live cell membranes. , 2017, Nature nanotechnology.

[7]  K. Salaita,et al.  Lighting Up the Force: Investigating Mechanisms of Mechanotransduction Using Fluorescent Tension Probes , 2015, Molecular and Cellular Biology.

[8]  J. Liphardt,et al.  Reversible Unfolding of Single RNA Molecules by Mechanical Force , 2001, Science.

[9]  J. Fredberg,et al.  Collective cell guidance by cooperative intercellular forces , 2010, Nature materials.

[10]  P. Friedl,et al.  Collective cell migration in morphogenesis, regeneration and cancer , 2009, Nature Reviews Molecular Cell Biology.

[11]  B. Rothen‐Rutishauser,et al.  Dynamics of Tight and Adherens Junctions Under EGTA Treatment , 2002, The Journal of Membrane Biology.

[12]  Yanrong Wu,et al.  DNA-based micelles: synthesis, micellar properties and size-dependent cell permeability. , 2010, Chemistry.

[13]  K. Salaita,et al.  A General Approach for Generating Fluorescent Probes to Visualize Piconewton Forces at the Cell Surface. , 2016, Journal of the American Chemical Society.

[14]  Sami Alom Ruiz,et al.  Mechanical tugging force regulates the size of cell–cell junctions , 2010, Proceedings of the National Academy of Sciences.

[15]  Cheng Zhu,et al.  DNA-based digital tension probes reveal integrin forces during early cell adhesion , 2014, Nature Communications.

[16]  Min Zhao,et al.  Collective cell migration: Implications for wound healing and cancer invasion , 2013, Burns & Trauma.

[17]  S. Bray.  Notch signalling in context , 2016, Nature Reviews Molecular Cell Biology.

[18]  J. Lévêque,et al.  Measurement of mechanical forces generated by skin fibroblasts embedded in a three-dimensional collagen gel. , 1991, The Journal of investigative dermatology.

[19]  Roger Guimerà,et al.  Control of cell-cell forces and collective cell dynamics by the intercellular adhesome , 2015, Nature Cell Biology.

[20]  T. Yanagida,et al.  A programmable DNA origami nanospring that reveals force-induced adjacent binding of myosin VI heads , 2016, Nature Communications.

[21]  F. Höök,et al.  Bivalent cholesterol-based coupling of oligonucletides to lipid membrane assemblies. , 2004, Journal of the American Chemical Society.

[22]  Farhan Chowdhury,et al.  Constructing modular and universal single molecule tension sensor using protein G to study mechano-sensitive receptors , 2016, Scientific Reports.

[23]  David R. Liu,et al.  A DNA-based molecular probe for optically reporting cellular traction forces , 2014, Nature Methods.

[24]  Enrico Gratton,et al.  Fluid Shear Stress on Endothelial Cells Modulates Mechanical Tension across VE-Cadherin and PECAM-1 , 2013, Current Biology.

[25]  Joe Tien,et al.  Mechanotransduction at cell-matrix and cell-cell contacts. , 2004, Annual review of biomedical engineering.

[26]  Beth L. Pruitt,et al.  E-cadherin is under constitutive actomyosin-generated tension that is increased at cell–cell contacts upon externally applied stretch , 2012, Proceedings of the National Academy of Sciences.

[27]  Wesley R. Legant,et al.  Microfabricated tissue gauges to measure and manipulate forces from 3D microtissues , 2009, Proceedings of the National Academy of Sciences.

[28]  Christopher S. Chen,et al.  Cells lying on a bed of microneedles: An approach to isolate mechanical force , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Tejal A. Desai,et al.  Efficient Targeting of Fatty-Acid Modified Oligonucleotides to Live Cell Membranes through Stepwise Assembly , 2014, Biomacromolecules.

[30]  D. Leckband,et al.  Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation. , 2011, Physiological reviews.

[31]  Christopher S. Chen,et al.  Mechanotransduction in development: a growing role for contractility , 2009, Nature Reviews Molecular Cell Biology.

[32]  William J Polacheck,et al.  Measuring cell-generated forces: a guide to the available tools , 2016, Nature Methods.

[33]  Taekjip Ha,et al.  Defining Single Molecular Forces Required to Activate Integrin and Notch Signaling , 2013, Science.

[34]  D. Irvine,et al.  Membrane Anchored Immunostimulatory Oligonucleotides for In Vivo Cell Modification and Localized Immunotherapy** , 2011, Angewandte Chemie.