Mechanical Counterbalance of Kinesin and Dynein Motors in a Microtubular Network Regulates Cell Mechanics, 3D Architecture, and Mechanosensing
Source abstract
Abstract
Microtubules (MTs) and MT motor proteins form active 3D networks made of unstretchable cables with rod-like bending mechanics that provide cells with a dynamically changing structural scaffold. In this study, we report an antagonistic mechanical balance within the dynein-kinesin microtubular motor system. Dynein activity drives the microtubular network inward compaction, while isolated activity of kinesins bundles and expands MTs into giant circular bands that deform the cell cortex into discoids. Furthermore, we show that dyneins recruit MTs to sites of cell adhesion, increasing the topographic contact guidance of cells, while kinesins antagonize it via retraction of MTs from sites of cell adhesion. Actin-to-microtubule translocation of septin-9 enhances kinesin-MT interactions, outbalances the activity of kinesins over that of dyneins, and induces the discoid architecture of cells. These orthogonal mechanisms of MT network reorganization highlight the existence of an intricate mechanical balance between motor activities of kinesins and dyneins that controls cell 3D architecture, mechanics, and cell-microenvironment interactions.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Microtubule and mitosis dynamics · Cellular Mechanics and Interactions · Advanced Materials and Mechanics
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20903, United States
Section on Mechanobiology, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States
Department of Cell and Developmental Biology, Vanderbilt Medical Center, University of Vanderbilt, Nashville, Tennessee 37232, United States
Department of Pharmacology, Penn State College of Medicine, Pennsylvania State University, Hummelstown, Pennsylvania 17036, United States
Department of Biochemistry & Molecular Biology, Penn State College of Medicine, Pennsylvania State University, Hershey, Pennsylvania 17033, United States
Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, New York 14620, United States
Funding
Food and Drug Administration · American Heart Association · National Institute of Biomedical Imaging and Bioengineering · Passano Foundation · National Institutes of Health · National Institute of General Medical Sciences · Department of Pharmacology, Penn State College of Medicine
References (100+)
Show source-provided references
1. 10.1073/pnas.070315310410.1073/pnas.0703153104 ↗
2. 10.1038/s41467-018-06005-710.1038/s41467-018-06005-7 ↗
3. 10.1103/PhysRevLett.79.449710.1103/PhysRevLett.79.4497 ↗
4. 10.1073/pnas.88.14.603310.1073/pnas.88.14.6033 ↗
5. 10.1073/pnas.14119959810.1073/pnas.141199598 ↗
6. 10.1096/fj.12-21144110.1096/fj.12-211441 ↗
7. 10.1016/j.devcel.2016.11.00910.1016/j.devcel.2016.11.009 ↗
8. 10.1073/pnas.161804111410.1073/pnas.1618041114 ↗
9. 10.1083/jcb.20130608510.1083/jcb.201306085 ↗
10. 10.1016/j.devcel.2008.05.01610.1016/j.devcel.2008.05.016 ↗
11. 10.1038/s41467-018-07290-y10.1038/s41467-018-07290-y ↗
12. 10.1083/jcb.20190715410.1083/jcb.201907154 ↗
13. 10.1126/scisignal.aan574810.1126/scisignal.aan5748 ↗
14. 10.1038/s41467-021-22985-510.1038/s41467-021-22985-5 ↗
15. 10.1101/2020.07.22.20520310.1101/2020.07.22.205203 ↗
16. 10.1083/jcb.20060106010.1083/jcb.200601060 ↗
17. 10.1016/j.bbamcr.2015.07.01610.1016/j.bbamcr.2015.07.016 ↗
18. 10.1126/science.aaf065910.1126/science.aaf0659 ↗
19. 10.1038/s41591-018-0046-210.1038/s41591-018-0046-2 ↗
20. 10.1242/jcs.18943110.1242/jcs.189431 ↗
21. 10.1083/jcb.20090911310.1083/jcb.200909113 ↗
22. 10.1242/jcs.18232910.1242/jcs.182329 ↗
23. 10.1080/15384101.2015.102652310.1080/15384101.2015.1026523 ↗
24. 10.1111/imr.1221410.1111/imr.12214 ↗
25. 10.1038/onc.2010.6810.1038/onc.2010.68 ↗
26. 10.1016/j.yexcr.2017.05.02410.1016/j.yexcr.2017.05.024 ↗
27. 10.1073/pnas.060803010410.1073/pnas.0608030104 ↗
28. 10.1021/acsnano.9b0994110.1021/acsnano.9b09941 ↗
29. 10.1073/pnas.96.17.966610.1073/pnas.96.17.9666 ↗
30. 10.1083/jcb.20131110410.1083/jcb.201311104 ↗
31. 10.1016/j.actbio.2017.11.03910.1016/j.actbio.2017.11.039 ↗
32. 10.1016/j.celrep.2018.09.03010.1016/j.celrep.2018.09.030 ↗
33. 10.1016/j.cub.2021.01.00210.1016/j.cub.2021.01.002 ↗
34. 10.1038/ncb328510.1038/ncb3285 ↗
35. 10.1016/j.celrep.2017.05.06410.1016/j.celrep.2017.05.064 ↗
36. 10.7554/eLife.1014010.7554/eLife.10140 ↗
37. 10.1242/jcs.108.8.276110.1242/jcs.108.8.2761 ↗
38. 10.1523/JNEUROSCI.1135-07.200710.1523/JNEUROSCI.1135-07.2007 ↗
39. 10.15252/embj.201910395710.15252/embj.2019103957 ↗
40. 10.1073/pnas.171511511510.1073/pnas.1715115115 ↗
41. 10.1073/pnas.100473610710.1073/pnas.1004736107 ↗
42. 10.3390/ijms2014348410.3390/ijms20143484 ↗
43. 10.1182/blood-2007-10-11884410.1182/blood-2007-10-118844 ↗
44. Thomas S. G. · 2019 · 4710.1016/B978-0-12-813456-6.00003-5 ↗
45. 10.1111/jth.1281910.1111/jth.12819 ↗
46. 10.1039/C7IB00152E10.1039/C7IB00152E ↗
47. 10.1038/ncomms1492310.1038/ncomms14923 ↗
48. 10.7554/eLife.2517410.7554/eLife.25174 ↗
49. 10.1083/jcb.20081004110.1083/jcb.200810041 ↗
50. 10.1016/B978-0-12-420138-5.00020-310.1016/B978-0-12-420138-5.00020-3 ↗
51. 10.1529/biophysj.105.07014410.1529/biophysj.105.070144 ↗
52. 10.1002/cm.2012610.1002/cm.20126 ↗
53. 10.1016/j.bpj.2016.04.03410.1016/j.bpj.2016.04.034 ↗
54. 10.1242/jcs.0068410.1242/jcs.00684 ↗
55. 10.1126/sciadv.abd595610.1126/sciadv.abd5956 ↗
56. 10.1073/pnas.161804111410.1073/pnas.1618041114 ↗
57. 10.1073/pnas.18135419810.1073/pnas.181354198 ↗
58. 10.1038/ncb133210.1038/ncb1332 ↗
59. 10.1091/mbc.e03-10-077010.1091/mbc.e03-10-0770 ↗
60. 10.1038/3853210.1038/38532 ↗
61. 10.1126/science.105975810.1126/science.1059758 ↗
62. 10.1111/j.1768-322X.1999.tb01090.x10.1111/j.1768-322X.1999.tb01090.x ↗
63. 10.1242/jcs.0091910.1242/jcs.00919 ↗
64. 10.7554/eLife.0094310.7554/eLife.00943 ↗
65. 10.1091/mbc.e05-06-054210.1091/mbc.e05-06-0542 ↗
66. 10.1074/jbc.M109.06824710.1074/jbc.M109.068247 ↗
67. 10.1016/j.molcel.2011.06.02710.1016/j.molcel.2011.06.027 ↗
68. 10.1038/ncb187810.1038/ncb1878 ↗
69. 10.1038/s41580-018-0067-110.1038/s41580-018-0067-1 ↗
70. 10.7554/eLife.1083710.7554/eLife.10837 ↗
71. 10.7554/eLife.1407610.7554/eLife.14076 ↗
72. 10.1091/mbc.E19-09-049110.1091/mbc.E19-09-0491 ↗
73. 10.1007/s10974-005-9054-110.1007/s10974-005-9054-1 ↗
74. 10.3892/ijmm.2011.86710.3892/ijmm.2011.867 ↗
75. 10.1091/mbc.e11-07-061110.1091/mbc.e11-07-0611 ↗
76. 10.1126/scisignal.aai919210.1126/scisignal.aai9192 ↗
77. 10.3390/cells906135110.3390/cells9061351 ↗
78. 10.15252/embj.20148879210.15252/embj.201488792 ↗
79. 10.1146/annurev.cellbio.20.012103.09462310.1146/annurev.cellbio.20.012103.094623 ↗
80. 10.1038/s42003-021-02653-610.1038/s42003-021-02653-6 ↗
81. 10.1038/s41467-021-22422-710.1038/s41467-021-22422-7 ↗
82. 10.1016/j.chembiol.2017.12.01410.1016/j.chembiol.2017.12.014 ↗
83. 10.1096/fasebj.13.9002.S22110.1096/fasebj.13.9002.S221 ↗
84. 10.1091/mbc.9.7.161310.1091/mbc.9.7.1613 ↗
85. 10.1002/iub.138410.1002/iub.1384 ↗
86. 10.1038/s41467-017-02230-810.1038/s41467-017-02230-8 ↗
87. 10.3233/JAD-18054710.3233/JAD-180547 ↗
88. 10.1016/j.cub.2021.03.06410.1016/j.cub.2021.03.064 ↗
89. 10.1038/ncomms353210.1038/ncomms3532 ↗
90. 10.1091/mbc.e05-03-026710.1091/mbc.e05-03-0267 ↗
91. 10.1002/cm.2148810.1002/cm.21488 ↗
92. 10.1083/jcb.20130806810.1083/jcb.201308068 ↗
93. 10.1038/s41419-019-1318-610.1038/s41419-019-1318-6 ↗
94. 10.1038/s41598-020-59824-410.1038/s41598-020-59824-4 ↗
95. 10.1101/2020.02.19.95452910.1101/2020.02.19.954529 ↗
96. 10.1074/jbc.M80496220010.1074/jbc.M804962200 ↗
97. 10.1101/2021.04.23.44120010.1101/2021.04.23.441200 ↗
98. 10.1016/j.bpj.2017.08.00910.1016/j.bpj.2017.08.009 ↗
99. 10.1016/j.cub.2006.09.01410.1016/j.cub.2006.09.014 ↗
100. 10.1083/jcb.20140505010.1083/jcb.201405050 ↗