Abstract
Cellular cargos, including lipid droplets and mitochondria, are transported along microtubules using molecular motors such as kinesins. Our current understanding arises from experimental and computational studies of cargos with rigidly attached motors, in contrast to many biological cargos that have lipid surfaces that may allow surface mobility of motors. We develop a coupled-viscosity mechanochemical 3D computational model to compare different motor arrangements and mobilities. We find that surface mobility can resolve contradictions between recent reports that cargo attachment and transport initiation in vivo occur on 1-10s timescales, and expected slower behavior based on cargo rotation timescales of 102-103s at cytoplasmic viscosities. Further, we show that organizational changes can optimize for different objectives: Cargos with clustered motors are transported efficiently, but are slow to bind to microtubules, whereas those with motors dispersed rigidly on their surface bind microtubules quickly, but are transported inefficiently. Finally, cargos with freely-diffusing motors have both fast binding and efficient transport, although less efficient than clustered motors. These results suggest that experimentally observed changes in motor organization may be a control point for transport, modulated either by adaptor proteins or changes in lipid composition.
Significance statement Many subcellular structures have fluid surfaces, meaning the molecules on their surface have the ability to rearrange, both randomly and under force. Transport of these subcellular cargos, which is driven by molecular motors, facilitates many fundamental biological processes, including cellular metabolism and pathways implicated in neuronal health. In this work, computational simulation is used to show how the fluidity of their surfaces results in new biophysical phenomena, including the ability to efficiently initiate transport. Since many previous experiments and simulations use rigid cargo, our work introduces a new paradigm for control points by which subcellular processes can be regulated.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵1 Center for Complex Biological Systems, University of California, Irvine
Update to title, and added new analysis of (previously published) binding rates.