Many cells need to directionally migrate in response to external stimuli in order to accomplish their versatile functional tasks ranging from embryogenesis to wound healing and immune responses. On the other hand, misguidance of cell migration contributes to the pathogenesis of Europe’s socioeconomic most relevant diseases including cancer, cardiovascular diseases and chronic inflammation and better understanding the fundamental mechanisms of cell migration is of direct clinical relevance.
While directional motion is typically dictated by chemotactic and haptotactic gradients, the actual motility within the organism is restricted by physical constraints, such as the presence of other cells and the extracellular matrix. Correspondingly, the ability to successfully navigate within confined environments in the presence of obstacles is an essential requirement for efficient cell migration within organisms.
Lamellipodia are sheet-like protrusions of dendritic actin networks at the leading edge of migrating cells and inevitably the first cellular structures that encounter obstacles within their path of migration. Despite the well-established role of actin-rich lamellipodia in cell migration, the fundamental question of how lamellipodial actin-networks integrate local mechanical cues, like encountered obstacles into directional decision-making remains poorly understood. In particular, it remains to be determined how network-intrinsic processing of mechanical cues affects cell navigation with complex microenvironments like tissue.
LammeliActin investigated this gap of knowledge by taking advantage of a combination of new experimental approaches. The data generated provides evidence for a yet unknown force generating actin-structure required for cell migration in confined microenvironments and paves the way for the development of novel pharmacological strategies to manipulate cell migration in vivo (Gaertner et al. in preparation).
