title: Molecular adaptations allow dynein to generate large collective forces inside cells.
abstract: 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.
authors: Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
authors: Arpan K
authors: AK
authors: Rai
authors: Ashim
authors: A
authors: Rai
authors: Avin J
authors: AJ
authors: Ramaiya
authors: Rupam
authors: R
authors: Jha
authors: Roop
authors: R
authors: Mallik
mesh_terms: D000818:Animals; D001692:Biological Transport; D001696:Biomechanical Phenomena; D001923:Brain Chemistry; D002460:Cell Line; D004023:Dictyostelium; D004398:Dyneins / Q000737:chemistry / Q000378:metabolism*; D006041:Goats; D016547:Kinesins; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008863:Microspheres; D008870:Microtubules / Q000378:metabolism; D052898:Optical Tweezers; D010588:Phagosomes / Q000378:metabolism*
chemical_list: D004398:Dyneins; D016547:Kinesins