Micropatterning as a tool to decipher cell morphogenesis and functions

Manuel Théry

doi:10.1242/jcs.075150

Abstract

In situ, cells are highly sensitive to geometrical and mechanical constraints from their microenvironment. These parameters are, however, uncontrolled under classic culture conditions, which are thus highly artefactual. Micro-engineering techniques provide tools to modify the chemical properties of cell culture substrates at sub-cellular scales. These can be used to restrict the location and shape of the substrate regions, in which cells can attach, so-called micropatterns. Recent progress in micropatterning techniques has enabled the control of most of the crucial parameters of the cell microenvironment. Engineered micropatterns can provide a micrometer-scale, soft, 3-dimensional, complex and dynamic microenvironment for individual cells or for multi-cellular arrangements. Although artificial, micropatterned substrates allow the reconstitution of physiological in situ conditions for controlled in vitro cell culture and have been used to reveal fundamental cell morphogenetic processes as highlighted in this review. By manipulating micropattern shapes, cells were shown to precisely adapt their cytoskeleton architecture to the geometry of their microenvironment. Remodelling of actin and microtubule networks participates in the adaptation of the entire cell polarity with respect to external constraints. These modifications further impact cell migration, growth and differentiation.

Highlights

Cells in situ, within organs or tissues, are embedded into a highly structured microenvironment
The biochemical composition and stiffness of the microenvironment specify the factors that can engage in cell adhesion, and thereby affect intracellular signalling pathways (Fig. 1)
Cell adhesion is the first cellular functional unit that responds to microenvironmental cues

Summary

Introduction

Within organs or tissues, are embedded into a highly structured microenvironment. The biochemical composition and stiffness of the microenvironment specify the factors that can engage in cell adhesion, and thereby affect intracellular signalling pathways (Fig. 1) These pathways subsequently dictate the assembly and dynamics of cytoskeleton networks. Cell adhesion is the first cellular functional unit that responds to microenvironmental cues It guides actin and microtubule networks assembly and, thereby, further orients the construction of cell internal architecture and establishment of cell polarity. Focal adhesions accumulate in the most distal regions of cell periphery, such as the apices of a triangle, where they grow and promote the formation of lamellipodia, filopodia and other membrane protrusions (Fig. 2) (Brock et al, 2003; Parker et al, 2002; Théry et al, 2005) Another important aspect of the physiological ECM network is that it is fibrillar and heterogeneous.

C Laser-patterning

A Dynamic micropattern