Cell Origami: Self-Folding of Three-Dimensional Cell-Laden Microstructures Driven by Cell Traction Force

This paper describes a method of generating three-dimensional (3D) cell-laden microstructures by applying the principle of origami folding technique and cell traction force (CTF). We harness the CTF as a biological driving force to fold the microstructures. Cells stretch and adhere across multiple microplates. Upon detaching the microplates from a substrate, CTF causes the plates to lift and fold according to a prescribed pattern. This self-folding technique using cells is highly biocompatible and does not involve special material requirements for the microplates and hinges to induce folding. We successfully produced various 3D cell-laden microstructures by just changing the geometry of the patterned 2D plates. We also achieved mass-production of the 3D cell-laden microstructures without causing damage to the cells. We believe that our methods will be useful for biotechnology applications that require analysis of cells in 3D configurations and for self-assembly of cell-based micro-medical devices.

[1]  George M. Whitesides,et al.  Microorigami: Fabrication of Small, Three-Dimensional, Metallic Structures , 2001 .

[2]  David H. Gracias,et al.  Patterning Thin Film Mechanical Properties to Drive Assembly of Complex 3D Structures , 2008 .

[3]  Barjor Gimi,et al.  Self-Assembled Three Dimensional Radio Frequency (RF) Shielded Containers for Cell Encapsulation , 2005, Biomedical microdevices.

[4]  I. Shimoyama,et al.  Insect-model based microrobot with elastic hinges , 1994 .

[5]  Zeeya Merali.  Profile: Zhong You. 'Origami engineer' flexes to create stronger, more agile materials. , 2011, Science.

[6]  Daisuke Shoji,et al.  Printed Origami Structures , 2010, Advanced materials.

[7]  K. Kuribayashi,et al.  Self-deployable origami stent grafts as a biomedical application of Ni-rich TiNi shape memory alloy foil , 2006 .

[8]  Sergio Pellegrino,et al.  The Folding of Triangulated Cylinders, Part III: Experiments , 1996 .

[9]  Leonid Ionov,et al.  Soft microorigami: self-folding polymer films , 2011 .

[10]  Isao Shimoyama,et al.  A design method for out-of-plane structures by multi-step magnetic self-assembly , 2006 .

[11]  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.

[12]  Ulrich S Schwarz,et al.  Cell-ECM traction force modulates endogenous tension at cell–cell contacts , 2011, Proceedings of the National Academy of Sciences.

[13]  David H Gracias,et al.  Three-dimensional fabrication at small size scales. , 2010, Small.

[14]  Evin Gultepe,et al.  Self-folding devices and materials for biomedical applications. , 2012, Trends in biotechnology.

[15]  K. Miura.  Concepts of Deployable Space Structures , 1993 .

[16]  David M J S Bowman,et al.  Flammable biomes dominated by eucalypts originated at the Cretaceous-Palaeogene boundary. , 2011, Nature communications.

[17]  M. Jamal,et al.  Self-folding immunoprotective cell encapsulation devices. , 2011, Nanomedicine : nanotechnology, biology, and medicine.

[18]  Biomechanical Contribution of Cytoskeletal Structures to Traction Forces in Cultured Smooth Muscle Cells , 2010 .

[19]  Jeong-Hyun Cho,et al.  Directed growth of fibroblasts into three dimensional micropatterned geometries via self-assembling scaffolds. , 2010, Biomaterials.

[20]  E. Yeatman,et al.  Demonstration of three-dimensional microstructure self-assembly , 1995 .

[21]  Takeo Matsumoto,et al.  Dynamic Change in Morphology and Traction Forces at Focal Adhesions in Cultured Vascular Smooth Muscle Cells During Contraction , 2011 .

[22]  I. Stewart.  Mathematics: Some assembly needed , 2007, Nature.

[23]  P. Rothemund.  Folding DNA to create nanoscale shapes and patterns , 2006, Nature.

[24]  M. Jamal,et al.  Self-folding micropatterned polymeric containers , 2011, Biomedical microdevices.

[25]  Ali Khademhosseini,et al.  Progress in tissue engineering. , 2009, Scientific American.

[26]  L. Ionov,et al.  Temperature controlled encapsulation and release using partially biodegradable thermo-magneto-sensitive self-rolling tubes , 2010 .

[27]  E. Smela,et al.  Microfabricating conjugated polymer actuators. , 2000, Science.

[28]  Vikramaditya G. Yadav,et al.  Cell and protein compatibility of parylene-C surfaces. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[29]  M. Jamal,et al.  Differentially photo-crosslinked polymers enable self-assembling microfluidics. , 2011, Nature communications.

[30]  Ebihara,et al.  Photoinduced graft polymerization of 2-methacryloyloxyethyl phosphorylcholine on polyethylene membrane surface for obtaining blood cell adhesion resistance. , 2000, Colloids and surfaces. B, Biointerfaces.

[31]  Hao Yan,et al.  DNA Origami with Complex Curvatures in Three-Dimensional Space , 2011, Science.

[32]  David H. Gracias,et al.  Self-loading lithographically structured microcontainers: 3D patterned, mobile microwells. , 2008, Lab on a chip.