Molecular Understanding of Cellular Behavior
Chemical control of adhesion, proliferation, signaling and phenotype
Cells may be controlled in terms of their adhesion and spreading by molecular interaction with membrane and surface receptors. Phenotypes can be modified by small molecules derived from molecular libraries. At CECB, we have developed screening technologies for selection of molecules that interact with receptors or directly with the cell membrane through "on bead" selection technologies using fluorescence as a readout. Using this approach, GPCR agonists have been identified. Moreover, super-adhesion molecules have been developed through iterative rounds of synthesis and screening of D-amino acid libraries (Figure 1). CECB intends to develop "on bead" screening for phenotypic changes of stem cells induced by peptidomimetic small molecules prepared in the form of split mix libraries. By combining cell adhesion with libraries of small molecule that modulate cell behavior and proliferation, compounds for use in cell development may be derived at high velocity. MPM-encoding technology and the development of stable on-bead fluorescence assays are essential to these studies.
Cellular adhesion of HEK293-cells, Jurkat-cells and E.Coli to PEGA-beads decorated with a D-amino acid heptapeptide adhesion molecules.