journal article·2024-10-29

Applying Spatiotemporal Modeling of Cell Dynamics to Accelerate Drug Development

Xindong Chen, Shihao Xu, Bizhu Chu, Jing Guo, Huikai Zhang, Shuyi Sun, Le Song, Xi-Qiao Feng

ACS Nano· Volume 18· Issue 43
Publisher page

Abstract

Cells act as physical computational programs that utilize input signals to orchestrate molecule-level protein-protein interactions (PPIs), generating and responding to forces, ultimately shaping all of the physiological and pathophysiological behaviors. Genome editing and molecule drugs targeting PPIs hold great promise for the treatments of diseases. Linking genes and molecular drugs with protein-performed cellular behaviors is a key yet challenging issue due to the wide range of spatial and temporal scales involved. Building predictive spatiotemporal modeling systems that can describe the dynamic behaviors of cells intervened by genome editing and molecular drugs at the intersection of biology, chemistry, physics, and computer science will greatly accelerate pharmaceutical advances. Here, we review the mechanical roles of cytoskeletal proteins in orchestrating cellular behaviors alongside significant advancements in biophysical modeling while also addressing the limitations in these models. Then, by integrating generative artificial intelligence (AI) with spatiotemporal multiscale biophysical modeling, we propose a computational pipeline for developing virtual cells, which can simulate and evaluate the therapeutic effects of drugs and genome editing technologies on various cell dynamic behaviors and could have broad biomedical applications. Such virtual cell modeling systems might revolutionize modern biomedical engineering by moving most of the painstaking wet-laboratory effort to computer simulations, substantially saving time and alleviating the financial burden for pharmaceutical industries.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Cellular Mechanics and Interactions · Cell Image Analysis Techniques · 3D Printing in Biomedical Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics

Tsinghua University

BioMap

School of Pharmacy

Shenzhen University

Medical School

Department of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research

The First Affiliated Hospital of Xiamen University

References (100+)

Show source-provided references
1. 10.1016/j.cell.2015.11.05710.1016/j.cell.2015.11.057 ↗
2. 10.1038/d41586-021-00018-x10.1038/d41586-021-00018-x ↗
3. 10.1016/bs.aams.2022.05.00410.1016/bs.aams.2022.05.004 ↗
4. 10.1073/pnas.230651212010.1073/pnas.2306512120 ↗
5. 10.1038/s42003-020-01335-z10.1038/s42003-020-01335-z ↗
6. 10.1038/s41586-020-2647-410.1038/s41586-020-2647-4 ↗
7. 10.1038/s41580-021-00424-z10.1038/s41580-021-00424-z ↗
8. 10.1016/j.cell.2017.07.05110.1016/j.cell.2017.07.051 ↗
9. 10.1126/science.aba289410.1126/science.aba2894 ↗
10. 10.1126/science.aba264410.1126/science.aba2644 ↗
11. 10.1038/s41556-021-00786-810.1038/s41556-021-00786-8 ↗
12. 10.1038/s41586-022-05394-610.1038/s41586-022-05394-6 ↗
13. 10.1016/j.cub.2018.07.02510.1016/j.cub.2018.07.025 ↗
14. 10.1103/PhysRevE.102.01240510.1103/PhysRevE.102.012405 ↗
15. 10.1016/j.bpj.2017.04.04410.1016/j.bpj.2017.04.044 ↗
16. 10.1126/sciadv.160303210.1126/sciadv.1603032 ↗
17. 10.1016/j.cell.2016.01.02110.1016/j.cell.2016.01.021 ↗
18. 10.1146/annurev-immunol-042718-04134110.1146/annurev-immunol-042718-041341 ↗
19. 10.1016/j.jim.2015.04.02910.1016/j.jim.2015.04.029 ↗
20. 10.1126/science.aam933510.1126/science.aam9335 ↗
21. 10.1038/s41467-019-10644-910.1038/s41467-019-10644-9 ↗
22. 10.1016/j.cell.2015.11.04810.1016/j.cell.2015.11.048 ↗
23. 10.1242/jcs.20273910.1242/jcs.202739 ↗
24. 10.1038/s41556-019-0414-210.1038/s41556-019-0414-2 ↗
25. 10.1038/s41467-022-31207-510.1038/s41467-022-31207-5 ↗
26. 10.1038/s41467-019-10751-710.1038/s41467-019-10751-7 ↗
27. 10.1038/s41563-019-0566-210.1038/s41563-019-0566-2 ↗
28. 10.1016/j.devcel.2017.08.00310.1016/j.devcel.2017.08.003 ↗
29. 10.1016/j.cub.2021.01.03610.1016/j.cub.2021.01.036 ↗
30. 10.1016/S0092-8674(03)00120-X10.1016/S0092-8674(03)00120-X ↗
31. 10.7554/eLife.4984010.7554/eLife.49840 ↗
32. 10.1073/pnas.161770511410.1073/pnas.1617705114 ↗
33. 10.3389/fimmu.2018.0228610.3389/fimmu.2018.02286 ↗
34. 10.1126/sciimmunol.aav544510.1126/sciimmunol.aav5445 ↗
35. 10.1158/1078-0432.CCR-05-256610.1158/1078-0432.CCR-05-2566 ↗
36. 10.1158/0008-5472.CAN-16-206010.1158/0008-5472.CAN-16-2060 ↗
37. 10.1016/j.devcel.2019.09.01810.1016/j.devcel.2019.09.018 ↗
38. 10.1038/nm.419710.1038/nm.4197 ↗
39. 10.1016/j.bbadis.2018.11.01410.1016/j.bbadis.2018.11.014 ↗
40. 10.1056/NEJMoa221294810.1056/NEJMoa2212948 ↗
41. 10.1038/d41586-022-00651-010.1038/d41586-022-00651-0 ↗
42. 10.1126/science.aat178010.1126/science.aat1780 ↗
43. Horwitz S. · Annals of oncology: official journal of the European Society for Medical Oncology · 1994 · 5 · S310.1093/annonc/5.suppl_4.S3 ↗
44. 10.1038/s41420-021-00453-910.1038/s41420-021-00453-9 ↗
45. 10.1038/s41467-020-18389-610.1038/s41467-020-18389-6 ↗
46. 10.1016/j.ejphar.2011.05.03610.1016/j.ejphar.2011.05.036 ↗
47. 10.1038/s41598-017-14722-010.1038/s41598-017-14722-0 ↗
48. 10.1016/j.cellsig.2009.12.01210.1016/j.cellsig.2009.12.012 ↗
49. 10.1093/jmcb/mjs01010.1093/jmcb/mjs010 ↗
50. 10.1038/s41375-020-0866-110.1038/s41375-020-0866-1 ↗
51. 10.1126/science.113759210.1126/science.1137592 ↗
52. 10.1126/science.119148410.1126/science.1191484 ↗
53. 10.1016/j.devcel.2021.08.00710.1016/j.devcel.2021.08.007 ↗
54. 10.1083/jcb.20060115910.1083/jcb.200601159 ↗
55. 10.1038/s41467-017-01745-410.1038/s41467-017-01745-4 ↗
56. 10.1126/science.aab350010.1126/science.aab3500 ↗
57. 10.1126/science.aad885710.1126/science.aad8857 ↗
58. 10.1126/science.aaq139210.1126/science.aaq1392 ↗
59. 10.1038/ncomms1609610.1038/ncomms16096 ↗
60. 10.1038/ncb352510.1038/ncb3525 ↗
61. 10.1073/pnas.060583710310.1073/pnas.0605837103 ↗
62. 10.1021/jacs.1c0622310.1021/jacs.1c06223 ↗
63. 10.1016/j.jmps.2020.10387210.1016/j.jmps.2020.103872 ↗
64. 10.1016/j.jmps.2021.10441910.1016/j.jmps.2021.104419 ↗
65. 10.1038/ncomms1032310.1038/ncomms10323 ↗
66. 10.1016/j.bpj.2018.09.01010.1016/j.bpj.2018.09.010 ↗
67. 10.1016/j.jhealeco.2016.01.01210.1016/j.jhealeco.2016.01.012 ↗
68. 10.1038/s41586-020-2117-z10.1038/s41586-020-2117-z ↗
69. 10.1016/j.cell.2018.03.01410.1016/j.cell.2018.03.014 ↗
70. 10.1016/j.jmb.2021.16735110.1016/j.jmb.2021.167351 ↗
71. 10.1038/s41586-019-1087-510.1038/s41586-019-1087-5 ↗
72. 10.1038/nrm.2017.13210.1038/nrm.2017.132 ↗
73. 10.1038/ncb349810.1038/ncb3498 ↗
74. 10.1038/s41467-023-36304-710.1038/s41467-023-36304-7 ↗
75. 10.1242/jcs.17614910.1242/jcs.176149 ↗
76. 10.1039/C6CS00636A10.1039/C6CS00636A ↗
77. 10.2174/18715201079472863910.2174/187152010794728639 ↗
78. Burke P. A. · Cancer Res. · 2002 · 62 · 4263
79. 10.1200/JCO.2008.16.751010.1200/JCO.2008.16.7510 ↗
80. 10.1158/1535-7163.MCT-08-098610.1158/1535-7163.MCT-08-0986 ↗
81. 10.1007/s00280-008-0724-810.1007/s00280-008-0724-8 ↗
82. 10.1358/dot.2020.56.9.317811010.1358/dot.2020.56.9.3178110 ↗
83. 10.1038/srep1964010.1038/srep19640 ↗
84. 10.1097/PPO.0b013e3182828d3810.1097/PPO.0b013e3182828d38 ↗
85. 10.1158/1535-7163.MCT-05-013010.1158/1535-7163.MCT-05-0130 ↗
86. 10.1158/0008-5472.CAN-10-144710.1158/0008-5472.CAN-10-1447 ↗
87. 10.1038/nature0356610.1038/nature03566 ↗
88. 10.1186/s12935-022-02624-910.1186/s12935-022-02624-9 ↗
89. 10.1006/bbrc.1999.112910.1006/bbrc.1999.1129 ↗
90. 10.1016/S0735-1097(02)02632-310.1016/S0735-1097(02)02632-3 ↗
91. 10.1126/science.109919010.1126/science.1099190 ↗
92. 10.1074/jbc.272.4.253410.1074/jbc.272.4.2534 ↗
93. 10.1038/s41467-019-09936-x10.1038/s41467-019-09936-x ↗
94. 10.1038/sj.bjc.660510110.1038/sj.bjc.6605101 ↗
95. 10.1158/1078-0432.CCR-16-066710.1158/1078-0432.CCR-16-0667 ↗
96. 10.1016/j.bbrc.2020.03.10210.1016/j.bbrc.2020.03.102 ↗
97. 10.1038/sj.bjc.660455910.1038/sj.bjc.6604559 ↗
98. 10.3109/02713683.2014.88845310.3109/02713683.2014.888453 ↗
99. Chuang J. C. · Translational Lung Cancer Research · 2015 · 4 · 639
100. 10.3390/ph1411112610.3390/ph14111126 ↗