Formin mDia1 senses and generates mechanical forces on actin filaments

• Published in: Nature communications 2013, Vol.4 (1), p.1883-1883, Article 1883
• Main Authors: Jégou, Antoine, Carlier, Marie-France, Romet-Lemonne, Guillaume
• Format: Article
• Language: English
• Subjects: 631/57/2272; 631/80/128/1276; Actin Cytoskeleton - metabolism; Adenosine Diphosphate - metabolism; Animals; Biomechanical Phenomena; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Humanities and Social Sciences; Humans; Mice; Microfluidics; multidisciplinary; Polymerization; Protein Multimerization; Protein Structure, Tertiary; Rabbits; Rheology; Science; Science (multidisciplinary); Viscosity
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms2888

Cytoskeleton assembly is instrumental in the regulation of biological functions by physical forces. In a number of key cellular processes, actin filaments elongated by formins such as mDia are subject to mechanical tension, yet how mechanical forces modulate the assembly of actin filaments is an open question. Here, using the viscous drag of a microfluidic flow, we apply calibrated piconewton pulling forces to individual actin filaments that are being elongated at their barbed end by surface-anchored mDia1 proteins. We show that mDia1 is mechanosensitive and that the elongation rate of filaments is increased up to two-fold by the application of a pulling force. We also show that mDia1 is able to track a depolymerizing barbed end in spite of an opposing pulling force, which means that mDia1 can efficiently put actin filaments under mechanical tension. Our findings suggest that formin function in cells is tightly coupled to the mechanical activity of other machineries. Formins are a family of protein complexes that accelerate actin filament nucleation and elongation. Jegou et al. show that the formin mDia1 can generate mechanical tension in actin filaments, while conversely, pulling forces applied by viscous drag increase formin elongation activity.