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For over four decades, the treadmilling model, where actin filaments elongate at barbed ends and
disassemble at pointed ends, has served as the central paradigm defining cellular actin dynamics.
Recent work from my laboratory has challenged its universality of this textbook model, revealing
that actin filament ends function as dynamic regulatory hubs controlled by the simultaneous action
of mechanical forces and multi-protein ecosystems.
To dissect these mechanisms, my lab integrates microfluidics-assisted single-molecule imaging
(mf-TIRF), force spectroscopy, quantitative biochemistry, structural biology, and theory. Our recent
studies have revealed that barbed ends are not strictly dedicated to growth. Instead, they can
undergo both assembly and disassembly through the coordinated actions of depolymerases,
capping proteins, and polymerases functioning within dynamic multi-protein ecosystems.
Conversely, we uncovered that pointed ends are capable of rapid elongation, a process long
thought impossible in vivo. We discovered that the Vibrio cholerae effector VopF functions as a
processive pointed-end polymerase whose activity is directly enhanced by piconewton-scale
tensile forces, establishing a novel mechanosensitive mode of actin assembly. More recently, we
identified the first eukaryotic mechanism of pointed-end elongation driven by Leiomodin-2
(Lmod2), revealing how thin filaments elongate in muscle cells despite capped barbed ends.
Together, our findings call for a re-evaluation of the classical treadmilling paradigm, establishing
mechanical forces and multi-protein interactions as central regulators of physiological actin
dynamics. |