Abstract
Cell migration on soft surfaces occurs in both physiological and pathological processes such as corticogenesis during embryonic development and cancer invasion and metastasis. The Arp2/3 complex in neural progenitor cells was previously demonstrated to be necessary for cell migration on soft elastic substrate but not on stiff surfaces, but the underlying mechanism was unclear. Here, we integrate computational and experimental approaches to elucidate how the Arp2/3 complex enables cell migration on soft surfaces. We found that lamellipodia comprised of a branched actin network nucleated by the Arp2/3 complex distribute forces over a wider area, thus decreasing stress in the substrate. Additionally, we found that interactions between parallel focal adhesions within lamellipodia prolong cell-substrate interactions by compensating for the failure of neighboring adhesions. Together with decreased substrate stress, this leads to the observed improvements in migratory ability on soft substrates in cells utilizing lamellipodia-dependent mesenchymal migration when compared with filopodia-based migration. These results show that the Arp2/3 complex-dependent lamellipodia provide multiple distinct mechanical advantages to gliomas migrating on soft 2D substrates, which can contribute to their invasive potential.