Abstract
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.
Highlights
Origami, the traditional Japanese art of paper folding, has remained popular over the centuries because it enables the production of various three-dimensional (3D) sculptures by folding two-dimensional (2D) sheets
Selective patterning of the cells on the microplates was achieved by coating the glass substrate areas, where the microplates do not exist, with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer; this polymer inhibits protein bridge them in order to fold the microplates by the cell traction force (CTF) (Figure 3A)
The spacing between the plates is a critical criterion that determines whether the cells can Folding of the microplates by CTF We experimentally investigated how the cells folded from 2D
Summary
The traditional Japanese art of paper folding, has remained popular over the centuries because it enables the production of various three-dimensional (3D) sculptures by folding two-dimensional (2D) sheets. The origami folding techniques have recently been explored to produce various 3D cell-laden microstructures including micro-sized containers [15,16,17,18,19,20,21] and scaffolds for artificial tissues [22,23] The folding of these microstructures is typically performed by surface tension [15,17], stress-induced forces [16,21,22,23], and shrinkage of the hinges [18,19] with external triggers such as temperature and electrical/chemical signals. The compatibility of the external triggers to living cells must be considered in these folding mechanisms
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