Micromechanical control of cell–cell interactions

Abstract

The development and function of living tissues depends largely on interactions between cells that can vary in both time and space; however, temporal control of cell-cell interaction is experimentally challenging. By using a micromachined silicon substrate with moving parts, we demonstrate the dynamic regulation of cell-cell interactions via direct manipulation of adherent cells with micrometer-scale precision. We thereby achieve mechanical control of both tissue composition and spatial organization. As a case study, we demonstrate the utility of this tool in deconstructing the dynamics of intercellular communication between hepatocytes and supportive stromal cells in coculture. Our findings indicate that the maintenance of the hepatocellular phenotype by stroma requires direct contact for a limited time (Ϸhours) followed by a sustained soluble signal that has an effective range of <400 m. This platform enables investigation of dynamic cell-cell interaction in a multitude of applications, spanning embryogenesis, homeostasis, and pathogenic processes.dynamic substrate ͉ intercellular communication ͉ microelectromechanical systems ͉ microenvironment ͉ microfabrication

Cellular and multicellular form and function☆

“…Patterned cells that are exposed to a newly adhesive surface form new adhesions and migrate away from the initial patterns [9]. (D) Microfabricated silicon combs dynamically control adhesion of cells to neighboring cells by changing from a contacting to separated configuration [10]. (A) Cells seeded on increasingly larger islands exhibit progressively higher rates of proliferation and lower rates of apoptosis [5].…”

“…In another study, interactions between cells of different types, or heterotypic contact, restores hepatocyte function in vitro [39]. Notably, microengineered tools were used to confirm that both the amount and duration of contact are both important parameters in contact-mediated maintainance of cell function [10].…”

“…Dynamic manipulation of cell-cell adhesion has recently been achieved. Cells were cultured directly onto microfabricated silicon devices that were oxidized, coated with polystyrene and then plasma treated to produce a surface comparable to tissue culture plastic [10]. Using such a microfabricated device, Hui and Bhatia created a substrate consisting of two interlocking parts, which can be placed in discrete configurations-with cells contacting or separated by a micronscaled gap ( Figure 1D) [10].…”

“…Cells were cultured directly onto microfabricated silicon devices that were oxidized, coated with polystyrene and then plasma treated to produce a surface comparable to tissue culture plastic [10]. Using such a microfabricated device, Hui and Bhatia created a substrate consisting of two interlocking parts, which can be placed in discrete configurations-with cells contacting or separated by a micronscaled gap ( Figure 1D) [10]. By culturing cells on these substrates and adjusting placement of the interlocking components, the effects of paracrine (transmitted through soluble factors) and juxtacrine signals (transmitted through contact) was examined.…”

A microfluidic array with cellular valving for single cell co-culture

“…A prime example was the use of interdigitated silicon combs for the controlled contact, or separation, of heterotypic populations. 8 Microfluidics can also be harnessed for reliable single cell handling. Commonly, cells injected within a flow are directed along the fluidic path of least resistance to sub-cellular-sized exits where they become mechanically anchored for analysis 9 or for high efficiency electroporation.…”