RT Journal Article SR Electronic T1 Actomyosin Dynamics Determine the Extension and Retraction of Filopodia on Neuronal Dendrites JF bioRxiv FD Cold Spring Harbor Laboratory SP 057919 DO 10.1101/057919 A1 Olena O. Marchenko A1 Sulagna Das A1 Ji Yu A1 Igor L. Novak A1 Vladimir I. Rodionov A1 Nadia Efimova A1 Tatiana Svitkina A1 Charles W. Wolgemuth A1 Leslie M. Loew YR 2016 UL http://biorxiv.org/content/early/2016/06/16/057919.abstract AB Impact Statement In this study, using a combination of computational and experimental approaches we show that a complex dynamic behavior of dendritic filopodia that is essential for synaptogenesis is explained by an interplay among forces generated by actin retrograde flow, myosin contractility, and substrate adhesion.Abstract Dendritic filopodia are actin-filled dynamic subcellular structures that sprout on neuronal dendrites during neurogenesis. The exploratory motion of the filopodia is crucial for synaptogenesis but the underlying mechanisms are poorly understood. To study the filopodial motility, we collected and analyzed image data on filopodia in cultured rat hippocampal neurons. We hypothesized that mechanical feedback among the actin retrograde flow, myosin activity and substrate adhesion gives rise to various filopodial behaviors. We have formulated a minimal one-dimensional partial differential equation model that reproduced the range of observed motility. To validate our model, we systematically manipulated experimental correlates of parameters in the model: substrate adhesion strength, actin polymerization rate, myosin contractility and the integrity of the putative microtubule-based barrier at the filopodium base. The model predicts the response of the system to each of these experimental perturbations, supporting the hypothesis that our actomyosin-driven mechanism controls dendritic filopodia dynamics.