Intracellular Transport

 

 

To function, cells must transport material relatively long distances (~microns) to specific locations.  Passive diffusion is too slow and imprecise, so cells rely on active transport by molecular motors. 

 

Molecular motors, including the myosin that powers muscle contraction, turn chemical energy into force or motion.  Inside a cell, they attach to liposomes -- small vesicles containing material to be transported -- which they then transport along the filamentous proteins (e.g. actin) that make up the "skeleton" of the cell (the cytoskeleton).  Though molecular motors have been studied in great detail at the single molecule level, it is unclear how they function in more realistic conditions, where multiple motors work together to move liposomes through the complex 3D cytoskeleton.

 

I have recently started working on this problem in collaboration with the Warshaw lab at the University of Vermont.  They create in vitro 3D actin networks that mimic the cytoskeleton, and observe specially constructed liposomes move through these networks, propelled by ~10 molecular motors.  I have developed a predictive model of this system.

 

Example

 

 

Movie 1. (Click on image, or here to play)  Myosin V motors (yellow cylinders) navigate a liposome cargo (blue) through a 3D intersection of actin filaments (green and red).  This is a simulation of experiments performed in the Warshaw lab, and discussed in publication 1, below.

Current Publications Relating to Intracellular Transport

 

 

1. Lombardo, A.T., S. R. Nelson, M. Y. Ali, G. G. Kennedy, K. M. Trybus, S. Walcott, and D. M. Warshaw, Myosin Va molecular motors manoeuvre liposome cargo through suspended actin filament intersections in vitro.  Nature Communications, Volume 8, Article Number 15692, 2017.  PDF

 

2. Walcott, S., Kad, N. M., Theoretical prediction of the run speed distribution for a molecular motor. ASME Conference Proceedings, Volume 2008, pages 437-446, 2008.  PDF

 

Collaborators

 

Andrew Lombardo

Dave Warshaw

Kathy Trybus