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

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.

Capillary-valve-based platform towards cell-on-chip mechanotransduction assays

“…On uncoated silicon, we have observed drastic cell detachment, even for low actuation frequencies. Furthermore, in order to use the platform for stretching and compression assays, the design of the chip should be slightly modified: The gap between the mobile and the immobile part should not exceed 8 m [31]. Improving cell adhesion to silicon substrate as well as cell bridging across the microplates will be crucial for future cell-on-chip experiments.…”

Mobile Microplates for Morphological Control and Assembly of Individual Neural Cells

“…Fabrication of Mobile Microplates : Mobile microplates utilizing photolithography techniques (Figure 2 a) were fabricated as described elsewhere [29][30][31][32] with a slight modifi cation. Briefl y, fi rst a clean, surfacehydrophilic glass with acetone and isopropanol washing was prepared followed by O 2 plasma treatment.…”

“…Our group has reported circle or square shape mobile microplates that enabled handling adherent cells such as fi broblasts, [29][30][31][32] hepatocytes, [ 29,31 ] and muscle cells. [ 30 ] We newly designed microplates composed of a circle and several protruding linear arms to have a function to control the morphology of a neural cell and also to be applicable in neural circuit engineering ( Figure 1 ). The microplates have a temperature-sensitive sacrifi cial layer underneath for detachment, and are arrayed on a cell nonadhesive background for selective cell adhesion (Figure 1 a).…”

A perspective on 4D bioprinting

“…Therefore, fusion of 3D printed tissue spheroids into certain shape is not considered as 4D bioprinting, because tissue fusion process is natural, unless the printed spheroids can hold its as-printed state and start to fuse upon external stimulation. Furthermore, in some reported cases [9] , cell contraction and cell migration for cell-driven selffolding and self-assembly is actually also a natural biological process. The folding of the cell origami is not a programmed design, also because the sequence of the folding planes is totally random, neither controlled nor repeatable.…”