Neural differentiation regulated by biomimetic surfaces presenting motifs of extracellular matrix proteins

Abstract

The interaction between cells and the extracellular matrix (ECM) is essential during development. To elucidate the function of ECM proteins on cell differentiation, we developed biomimetic surfaces that display specific ECM peptide motifs in a controlled manner. Presentation of ECM domains for collagen, fibronectin, and laminin influenced the formation of neurites by differentiating PC12 cells. The effect of these peptide sequences was also tested on the development of adult neural stem/progenitor cells. In this system, collagen I and fibronectin induced the formation of beta-III-tubulin positive cells, whereas collagen IV reduced such differentiation. Biomimetic surfaces composed of multiple peptide types enabled the combinatorial effects of various ECM motifs to be studied. Surfaces displaying combined motifs were often predictable as a result of the synergistic effects of ECM peptides studied in isolation. For example, the additive effects of fibronectin and laminin resulted in greater expression of beta-III-tubulin positive cells, whereas the negative effect of the collagen IV domain was canceled out by coexpression of collagen I. However, simultaneous expression of certain ECM domains was less predictable. These data highlight the complexity of the cellular response to combined ECM signals and the need to study the function of ECM domains individually and in combination.

Role of Extracellular Matrix Renal Tubulo-interstitial Nephritis Antigen (TINag) in Cell Survival Utilizing Integrin αvβ3/Focal Adhesion Kinase (FAK)/Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B-Serine/Threonine Kinase (AKT) Signaling Pathway

“…7), suggesting that TINag provides a significant cellular protection. Because TINag binds with type IV collagen and laminin, one may anticipate that such protein/protein interactions may have an additive effect on the cellular homeostasis, as described in experiments with neuronal cells grown on biomimetic surfaces having motifs of different ECM proteins (16,40). However, the cells maintained on combined substrata, TINag ϩ type IV collagen or ϩ laminin, did not exhibit any synergistic effect.…”

Effects of Olig2-Overexpressing Neural Stem Cells and Myelin Basic Protein-Activated T Cells on Recovery from Spinal Cord Injury

“…Cell differentiation is regulated by various factors such as inherent differentiation potential and interactions between cells and the extracellular microenvironment [16][17][18][19]. Following SCI, the local microenvironment of the injured spinal cord is more complex, which includes natural elements of the spinal cord itself, as well as inflammatory cytokines and cytotoxic substances that have been produced in response to the trauma [20][21][22].…”

Oriented, Multimeric Biointerfaces of the L1 Cell Adhesion Molecule: An Approach to Enhance Neuronal and Neural Stem Cell Functions on 2-D and 3-D Polymer Substrates

“…However, the effective integration of neuronal bioactivity along with transplantable substrate designs remains a major challenge. Conventional bioactive or biomimetic substrates for neural engineering applications have presented peptides, extracellular matrix (ECM) proteins, growth factors, and cell adhesion proteins [5][6][7][8][9].…”