TY - JOUR
T1 - Molecular adaptations allow dynein to generate large collective forces inside cells
AU - Rai, Arpan K.
AU - Rai, Ashim
AU - Ramaiya, Avin J.
AU - Jha, Rupam
AU - Mallik, Roop
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/1/7
Y1 - 2013/1/7
N2 - Many cellular processes require large forces that are generated collectively by multiple cytoskeletal motor proteins. Understanding how motors generate force as a team is therefore fundamentally important but is poorly understood. Here, we demonstrate optical trapping at single-molecule resolution inside cells to quantify force generation by motor teams driving single phagosomes. In remarkable paradox, strong kinesins fail to work collectively, whereas weak and detachment-prone dyneins team up to generate large forces that tune linearly in strength and persistence with dynein number. Based on experimental evidence, we propose that leading dyneins in a load-carrying team take short steps, whereas trailing dyneins take larger steps. Dyneins in such a team bunch close together and therefore share load better to overcome low/intermediate loads. Up against higher load, dyneins "catch bond" tenaciously to the microtubule, but kinesins detach rapidly. Dynein therefore appears uniquely adapted to work in large teams, which may explain how this motor executes bewilderingly diverse cellular processes.
AB - Many cellular processes require large forces that are generated collectively by multiple cytoskeletal motor proteins. Understanding how motors generate force as a team is therefore fundamentally important but is poorly understood. Here, we demonstrate optical trapping at single-molecule resolution inside cells to quantify force generation by motor teams driving single phagosomes. In remarkable paradox, strong kinesins fail to work collectively, whereas weak and detachment-prone dyneins team up to generate large forces that tune linearly in strength and persistence with dynein number. Based on experimental evidence, we propose that leading dyneins in a load-carrying team take short steps, whereas trailing dyneins take larger steps. Dyneins in such a team bunch close together and therefore share load better to overcome low/intermediate loads. Up against higher load, dyneins "catch bond" tenaciously to the microtubule, but kinesins detach rapidly. Dynein therefore appears uniquely adapted to work in large teams, which may explain how this motor executes bewilderingly diverse cellular processes.
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U2 - 10.1016/j.cell.2012.11.044
DO - 10.1016/j.cell.2012.11.044
M3 - Article
C2 - 23332753
AN - SCOPUS:84872506411
VL - 152
SP - 172
EP - 182
JO - Cell
JF - Cell
SN - 0092-8674
IS - 1-2
ER -