The invention relates to methods for screening compounds for their ability to modulate actin polymerization. The invention is also related to compounds which modulate actin polymerization. More specifically, the invention is related to methods of screening compounds which modulate the interaction of cortactin or HS-1 with Arp2/3. The invention is also related to compounds which modulate the interaction of cortactin of HS1 with Arp2/3. Also provided are mutants of cortactin with decreased ability to interact with Arp2/3.