Macro-to-Micro Interface for the Control of Cellular Organization

Abstract

The spatial organization of cellular communities plays a fundamental role in determining intercellular communication and emergent behavior. However, few tools exist to modulate tissue organization at the scale of individual cells, particularly in the case of dynamic manipulation. Micromechanical reconfigurable culture achieves dynamic control of tissue organization by culturing adherent cells on microfabricated plates that can be shifted to reorganize the arrangement of the cells. While biological studies utilizing this approach have been previously reported, this paper focuses on the engineering of the device, including the mechanism for translating manual manipulation to precise microscale position control, fault-tolerant design for manufacture, and the synthetic-to-living interface.

A screen for short-range paracrine interactions

“…Due to the limited surface area of the comb device, 5 cells needed to be pooled from up to 18 combs per condition in order to obtain sufficient RNA quantity. Sample volume was a particular issue for the fibroblasts, which yielded less total RNA than the tumor cells.…”

“…As previously described, the comb device includes a self-alignment mechanism that enables a gap of 79 AE 1 mm to be repeatedly achieved by simple manual manipulation. 5 After 48 h, comb pairs were decoupled, quickly washed in PBS, and grouped with other combs from the same experimental conditions. Cells were then lysed off the combs and collected.…”

“…3–5 In this system, cells are grown on interdigitating sliding plates that can be positioned such that two populations are either in direct contact or separated by an 80-µm gap (Fig. 1a).…”

“…Previously, we described the use of microfabricated comb substrates for the study of heterotypic cell-cell signaling in liver cultures. [3][4][5] In this system, cells are grown on interdigitating sliding plates that can be positioned such that two populations are either in direct contact or separated by an 80 mm gap (Fig. 1a).…”