Tuning collective protein interactions using programmable DNA nanostructures
The emergence of collective movement, as in stellar streaming, flocks of birds, and ant colonies, is a widespread phenomenon across all scales. At the cellular level, the collective movement of myosins motors drives cell division, membrane trafficking, and muscle contraction. Understanding collective movements of myosin motors from whole-cell systems is challenging because the overly-complex cellular environment obscures the underlying interactions governing the higher order functions.
To systematically dissect cellular dynamics of motor proteins, we engineered two model systems consisting of programmable DNA nanostructures, patterned with precise numbers, types, and spatial arrangements of purified myosin motors. First, we use rectangular DNA origami nanostructures to dissect the tug-of-war in motor protein ensembles with opposite polarity myosin motors. Second, we use DNA nanotubes as platforms for engineering artificial thick filaments, the basic contractile unit of muscle, to reveal the behavior of a large number of myosin motors. Beyond controlling the spatial arrangement of myosin motors, we use DNA nanotubes as mechanical sensors for forces at short length scales and fast time scales that would be difficult to investigate by other means. These studies uncover elegant engineering principles for designing force sensors and molecular transporters on complex landscapes. Further, these DNA nanostructures can serve as platforms to reconstitute other emergent systems in molecular biology and far-from-equilibrium systems in soft condensed matter physics.
Finally, I will conclude with a discussion on the transformative potential and future directions, including the biological physics of malaria parasite invasion and mechanically active nanostructures for solving protein structures under defined tension.
Rizal F. Hariadi, Ph.D.
Wyss Institute for Biologically Inspired Engineering at Harvard University
Chalk talk, Friday, January 15th, at 9:30 in G-417.
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