Synergy between Laminin-Derived Elastin-like Polypeptides (LELPs) Optimizes Cell Spreading

Biomacromolecules. 2024 Jul 8;25(7):4001-4013. doi: 10.1021/acs.biomac.4c00144. Epub 2024 May 30.

Abstract

A major component of the extracellular matrix (ECM), laminins, modulates cells via diverse receptors. Their fragments have emerging utility as components of "ECM-mimetics" optimized to promote cell-based therapies. Recently, we reported that a bioactive laminin peptide known as A99 enhanced cell binding and spreading via fusion to an elastin-like polypeptide (ELP). The ELP "handle" serves as a rapid, noncovalent strategy to concentrate bioactive peptide mixtures onto a surface. We now report that this strategy can be further generalized across an expanded panel of additional laminin-derived elastin-like polypeptides (LELPs). A99 (AGTFALRGDNPQG), A2G80 (VQLRNGFPYFSY), AG73 (RKRLQVQLSIRT), and EF1m (LQLQEGRLHFMFD) all promote cell spreading while showing morphologically distinct F-actin formation. Equimolar mixtures of A99:A2G80-LELPs have synergistic effects on adhesion and spreading. Finally, three of these ECM-mimetics promote the neurite outgrowth of PC-12 cells. The evidence presented here demonstrates the potential of ELPs to deposit ECM-mimetics with applications in regenerative medicine, cell therapy, and tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Adhesion* / drug effects
  • Elastin* / chemistry
  • Elastin-Like Polypeptides
  • Extracellular Matrix / chemistry
  • Extracellular Matrix / metabolism
  • Laminin* / chemistry
  • Laminin* / pharmacology
  • PC12 Cells
  • Peptides / chemistry
  • Peptides / pharmacology
  • Rats

Substances

  • Laminin
  • Elastin
  • Peptides
  • Elastin-Like Polypeptides