Cell architectureThe physiological cell microenvironment consists of extracellular matrix (ECM) fibres, adjacent cells and extracellular fluids, and the cell adhesion machinery is the first cellular component to encounter it. Upon binding of extracellular ligands, localised signalling is induced with subsequent assembly of the cytoskeleton. These localised events will affect the entire cell architecture, because the intracellular space is physically connected and
SummaryIn 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.
Journal of Cell Sciencemechanically supported by a dynamic equilibrium (Ingber, 2003; Ingber, 2006).
Integrin-based cell adhesionIntegrins are transmembrane receptors that bind to ECM proteins and to intracellular actin filaments. When cells contact the ECM, they change their shape and spread in a multi-step process that includes cell attachment, formation of membrane protrusion, extension of cell membrane, and formation and contraction of stress fibers, which further stimulate cell attachment, membrane protrusion and cell shape extension.The attachment of the actin cytoskeleton to cell adhesions requires integrin clustering. Nanopatterning methods have led to determine the maximum distance of 60 nm between integrin molecules -a distance that still allows intracellular recruitment of actin filaments and signalling molecules (Arnold et al., 2004). Arrays of adhesive dots have been used to study the formation of filopodia and subsequent spreading steps. Depending on the cell type and the level of Rac activation, cells need a minimal distance between adhesion sites, so that filopodia can bridge them and promote cell spreading (Guillou et al., 2008;Lehnert et al., 2004). Th...