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

Figure 2

Interactions of the cell structures with adhesive matrix epitopes: from cell-size scale to nanoscale. (a) Certain events of matrix perception by the cell occur on scale comparable with size of the cell. Cells distinguish between 2D and 3D presentations of the epitopes. In case when 3D matrix is presented only from the basal side of the cell, thickness of the matrix layer can be critical for cell perception of the matrix. Cell perception of the underlying matrix thickness ranges approximately from 5 to 20 micrometers, which is comparable with average cell diameter. In cases when matrix defines the geometrical properties of cell adhesion surface, such as in case of adhesion islands model, adhesion area and shape can be influential factors for stem cell behavioral choices. (b) Cell propagates and spreads on the matrix due to spreading of filopodia, which form stable adhesion contacts with the matrix. In order to achieve stability of such adhesion contact, it takes not a single epitope but cluster of epitopes which, in turn, enable clustering of cell receptors and signaling to the cell. The following parameters of epitope clusters may be important to influence cell behavioral choices: number of epitopes per cluster, space between clusters, and so forth. Topography on micro- and nanoscale can also be influential on cell behavior. (c) Such events like co-signaling (synergy between the different cell receptors, i.e., receptor for matrix epitopes and receptor for growth factors) occur on even smaller scale. Importantly, the natural matrix adhesion molecules are very large ones (molecular weight up to 1 million Daltons, length up to 300 nanometers), compared to typical adhesion peptides (composed of several amino acids, with molecular weight below 1 thousand Daltons). Apparently, one has to consider geometry of functional clusters of receptors and matrix molecules on molecular level. (d) Affinity and specificity of matrix adhesion epitopes interactions with cell receptors occur on even smaller scale.