Neural differentiation regulated by biomimetic surfaces presenting motifs of extracellular matrix proteins.
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.
Cooke
M J
MJ
North East England Stem Cell Institute (NESCI), School of Biological and Biomedical Science, University of Durham, South Road, Durham DH1 3LE, United Kingdom.
Zahir
T
T
Phillips
S R
SR
Shah
D S H
DS
Athey
D
D
Lakey
J H
JH
Shoichet
M S
MS
Przyborski
S A
SA
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D016716:PC12 Cells; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D013499:Surface Properties / Q000187:drug effects
D016326:Extracellular Matrix Proteins