Small-Molecule-Induced Clustering of Heparan Sulfate Promotes Cell Adhesion

Adhesamine is an organic small molecule
that promotes adhesion
and growth of cultured human cells by binding selectively to heparan
sulfate on the cell surface. The present study combined chemical,
physicochemical, and cell biological experiments, using adhesamine
and its analogues, to examine the mechanism by which this dumbbell-shaped,
non-peptidic molecule induces physiologically relevant cell adhesion.
The results suggest that multiple adhesamine molecules cooperatively
bind to heparan sulfate and induce its assembly, promoting clustering
of heparan sulfate-bound syndecan-4 on the cell surface. A pilot study
showed that adhesamine improved the viability and attachment of transplanted
cells in mice. Further studies of adhesamine and other small molecules
could lead to the design of assembly-inducing molecules for use in
cell biology and cell therapy.