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 to 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.

VCD thermal equilibrium spectroscopic studies are supported by NMR-based structures and DFT modeling. MD dynamics simulations are correlated with IR-detected temperature-jump kinetics. These all have b-sheet structures, but differ in stabilities for different turns and aromatic contacts. DFT computations for an Ala-based structure with NMR constrained f,c angles yield IR and VCD simulations consistent with experimental data. The structures are sharply twisted with the first hairpin being better formed. Aromatic stabilization was energetically effective for Trp-Tyr on strands 1-2, less on strands 2-3, but a similar sequence with no aromatic interactions formed better sheets. MD studies show bistable fluctuation in the D Pro-Gly turns from Type 1' to 2', but Aib-Gly turns, with less torsional barrier, sampled more forms. These behaviors were evident in site-selected IR-detected T-jump relaxation kinetics. Isotopic labeling allows selected monitoring of turns and strands, and Aib-Gly have less spectral interference than D Pro-Gly turns. Equilibrium IR as well as T-jump dynamics reflect higher stabilities for strand 1-2 interactions.