Following the footprints of variability during filopodia growth

DANIELA SENRA; ALEJANDRA PAEZ; GERALDINE GUERON; LUCIANA BRUNO; NARA GUISONI

EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS

SPRINGER

Lugar: Berlin; Año: 2020

0175-7571

Filopodia are actin-built finger-like dynamic structures that pro-9 trude from the cell cortex. These structures can sense the environment and play10 key roles in migration and cell-cell interactions. The growth-retraction cycle of11 filopodia is a complex process exquisitely regulated by intra- and extra-cellular12 cues, whose nature remains elusive. Filopodia present wide variation in length,13 lifetime and growth rate. Here, we investigate the features of filopodia pat-14 terns in fixed prostate cancer cells by confocal microscopy. Analysis of almost15 a thousand filopodia suggests the presence of two different populations: one16 characterized by a narrow distribution of lengths and the other with a much17 more variable pattern with very long filopodia. We explore a stochastic model18 of filopodia growth which takes into account diffusion and reactions involving19 actin and the regulatory proteins formin and capping, and retrograde flow. In-20 terestingly, we found an inverse dependence between the filopodial length and21 the retrograde velocity. This result led us to propose that variations in the22 retrograde velocity could explain the experimental lengths observed for these23 tumor cells. In this sense, one population involves a wider range of retrograde24 velocities than the other population, and also includes low values of this ve-25 locity. It has been hypothesized that cells would be able to regulate retrograde26 flow as a mechanism to control filopodia length. Thus, we propound that the27 experimental filopodia pattern is the result of differential retrograde velocities28 originated from heterogeneous signaling due to cell-substrate interactions or29 prior cell-cell contacts.