Capturing extracellular matrix properties in vitro: Microengineering materials to decipher cell and tissue level processes

Abstract

Rapid advances in biology have led to the establishment of new fields with tremendous translational potential including regenerative medicine and immunoengineering. One commonality to these fields is the need to extract cells for manipulation in vitro; however, results obtained in laboratory cell culture will often differ widely from observations made in vivo. To more closely emulate native cell biology in the laboratory, designer engineered environments have proved a successful methodology to decipher the properties of the extracellular matrix that govern cellular decision making. Here, we present an overview of matrix properties that affect cell behavior, strategies for recapitulating important parameters in vitro, and examples of how these properties can affect cell and tissue level processes, with emphasis on leveraging these tools for immunoengineering.

Keywords: Biomaterials; extracellular matrix; micropatterning.

Figure 1

Matrix properties affect cell behavior in vitro: elasticity—MSC morphology (and cytokine secretions) is dependent on matrix stiffness. Composition—MSC differentiation is highly dependent on the matrix protein conjugated to the surface (reprinted by Lee et al., Copyright (2013), with permission from Elsevier). Ligand presentation—fibroblast focal adhesions only form on 5 µm RGD functionalized gold islands with stress fibers running between adhesions (reprinted with permission by Aydin et al., copyright (2010) American chemical society). Dynamics and degradation—cell adhesion can be switched on and off by switching the conjugation of ligands at the surface (reprinted by DeForest and Anseth, Copyright (2012), with permission from Wiley). Topography—substrate topography controls alignment and epigenetic reprogramming of cells (reprinted by permission from Macmillan Publishers Ltd: Nature Materials by Downing et al., copyright (2013)). Cell Shape—modifying cell shape can affect MSC cytoskeleton, focal adhesion formation and differentiation. (A color version of this figure is available in the online journal.)

Figure 2

Interactions of multiple cells. Several factors are introduced when multiple cells are considered together including cell–cell contact, contact between different cell types, the introduction of interfaces and curvature, and cytokine gradients across the system. These factors control effects such as collective cell behavior and cell sorting, for example. (A color version of this figure is available in the online journal.)