Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research

Figure 1

Physical, spatial, and molecular aspects of extracellular matrix that are known to affect stem cell behavioral patterns and choices. Extracellular matrix (ECM) of mammalian tissues in vivo is a complex structure composed of multiple molecular components, such as fibrils, fibril-associated crosslinking elements, and specific ligands interacting with cell receptors. Such molecular complexity has a biological reason, since lack of ECM molecules, due to mutation or knockout, often results in pathology or even mortality. Molecular composition of a matrix composition and the way of structural arrangement of the molecular components determine the physical, spatial, and molecular characteristics of the scaffold which, as we demonstrate in the review, may actively affect stem cells behavioral patterns. Physical aspects include stiffness (or elasticity); viscoelasticity; pore size and porosity; amplitude of static and dynamic deformations of the matrix (tensile, compressive, or shear); and frequency of cyclic deformations. Due to complex organization, elastic properties of the natural ECM cannot be characterized by a single parameter of Young’s modulus (which is valid for many synthetic gels). The stress-strain relation is often nonlinear and is described by stress-strain curve; the natural ECM tend to rearrange their structure under stress, which makes them viscoelastic and prone to plastic deformation. Viscoelastic materials change their elastic properties when they are subject to static strains or cyclic (dynamic) deformations; therefore, one has to take tensile characteristics of the system into account. Spatial arrangement includes dimensionality (2D or 3D) of the scaffold introduced to the cell; thickness of the substrate layer underlying the cell; cell polarity; surface area and geometry of adhesion surface; microscale topography of the surface; epitope concentration; epitope clustering characteristics (number of epitopes per cluster, spacing between epitopes within cluster, spacing between separate clusters, cluster patterns, and order or disorder in epitope arrangement); size, shape, and level of disorder of nanotopographical features such as fibers diameter and orientation. Molecular properties concern structural complexity of ECM molecules, types of adhesion epitopes and corresponding receptors, co-signaling (cooperation of growth factor- and matrix-dependent receptors), and affinity interactions.