Molecular spiders eat less and slow down with time

Molecular motors are biological nanomachines involved in almost every aspect of cellular life. Inspired by these and to better understand and control motion at the nanoscale, an emerging area of research involves the synthesis of novel molecular motors from biomolecular building blocks. To guide the understanding of experimental results and provide predictions of future motor performance, computer simulations have provided insight into novel mechanisms exhibited by so-called molecular spiders, a multilegged sub-class of synthetic motors.

HFSP Program Grant Award holders Nancy Forde, Heiner Linke and Paul Curmi and colleagues

Molecular motors are involved in almost every aspect of cellular life, including transport and communication, replication and transcription, and protein synthesis and degradation. Through extensive biochemical and biophysical investigations, the mechanisms by which these motors operate are being uncovered. These nanoscale machines operate in an environment dominated by random thermal motion, yet are capable of transducing chemical energy into mechanical work and directed motion far more efficiently than man-made macroscale machines. An emerging field is focusing on the creation of novel molecular motors, using biological molecules as building blocks to better understand and control motion at the nanoscale.

One class of synthetic motor is the so-called “molecular spider”, a machine that operates through binding of its legs to specific substrates presented on a surface.  The spider legs cleave (cut) the substrates, thereby releasing chemical energy, and then step along the surface preferentially to sites that have not yet been cleaved.  (An analogy to this would be a self-propelled lawnmower that moves to uncut grass, fueled by grass clippings.) Experimental studies have demonstrated that spiders are capable of taking multiple steps to move from the start to the end of a linear track of substrate, and have shown that the speed by which they move and the number of steps they take depends on the number of legs and the strength of their binding to the track. Now, computer simulations reveal for the first time how these spiders might perform as motors, by using the chemical kinetics of interactions of spider legs with their track to predict their ability to transport cargo against external loads.

This study has uncovered a property of motors heretofore not probed experimentally: a time-dependence to their motor properties. A population of spiders, placed initially at a starting line on a substrate track, will gradually lose coherence, with some spiders stepping forwards faster than others, while some step backwards. This arises for a number of reasons: the randomness associated with the underlying chemical kinetics; the ability of a spider to step across a substrate without cutting it; and the spider’s ability to step backwards into a previously cut part of the track. As time increases, this distribution further widens, and only those spiders able to move in lock-step with the boundary between cut and uncut sections of the track display ideal motor behaviour.

The research furthermore investigated how the motor properties depend on experimentally tunable parameters such as the number of spider legs and their span (how far apart they can bind on the track). Through appropriate selection of experimental building blocks, it is possible to increase the efficiency of the spiders (how much work they can do against an applied load), and the simulations make predictions of the values of efficiency attainable. Not surprisingly, spiders are less efficient than canonical biological motors such as kinesin or myosin that are able to use strategic conformational changes induced by interactions with their substrates to guide directed motion. The time-dependent mechanism, however, is likely to be directly relevant to the understanding of other biological molecular motors such as collagenases, which cut their collagen substrates and appear to undergo directed motion in searching for their next cleavage site. The combination of simulations and experiments offers a powerful approach to predict and test our understanding of how to achieve efficient directed motion at the nanoscale.

 

Figure (a): Initially, spiders (blue) are placed at a starting site on a track, with substrates (green circles) located to the right and products (open circles) to the left. Here, for comparison, kinesin motors (yellow) are shown at an initial position on a microtubule track.

    

Figure (b):  In contrast to kinesin motors, which are known to exhibit unidirectional stepping with little randomness (a small spread in average speeds), spiders are less ballistic in their motion, and the population increasingly loses coherence with time. On average, however, a population of spiders does exhibit motor properties, tending to move towards the right and able to do so against applied load forces. 

Reference

Time-dependent motor properties of multipedal molecular spiders. L. Samii, G.A. Blab, E.H.C. Bromley, H. Linke, P.M.G. Curmi, M.J. Zuckermann and N.R. Forde, Physical Review E, 84, 031111 (2011).

Other References

Experimental studies of the molecular spider:

Behavior of polycatalytic assemblies in a substrate-displaying matrix.  R. Pei, S.K. Taylor, D. Stefanovic, S. Rudchenko, T.E. Mitchell and M. Stojanovic. Journal of the American Chemical Society 128, 12693-12699 (2006). 

Molecular robots guided by prescriptive landscapes. K. Lund, A.J. Manzo, N. Dabby, N. Michelotti, A. Johnson-Buck, J. Nangreave, S. Taylor, R. Pei, M.N. Stojanovic, N.G. Walter, E. Winfree, H. Yan. Nature 465, 206-210 (2010).

 Physical Review link (Abstract for Time-dependent motor properties of multipedal molecular spiders)