Research

Theoretical Biophysics

Image of a fruit fly (Drosophila melanogaster) atop a plant. Photo by Géry Parent

Specialization

Biophysics lies at the intersection of two disciplines with vastly different approaches and nomenclatures; however, it is also an area ripe with opportunities for collaborative projects and unsaturated avenues of research. I am focused on one such avenue: exploring how mechanical stress and feedback play into the development of multicellular organisms. A full understanding of biological growth requires elucidation of how cells use mechanical stress fields to harmonize their activities.

Experimental investigations of the mechanical aspects of biological development are restricted by limitations in current technology. This is especially true in terms of evaluating the stress fields that permeate developed tissues and developing embryos. I overcome these limitations through dynamic system modeling: representing embryonic tissues as a mechanically active media and then using the model to perform experiments. Working with experimental collaborators provides meaningful insight, and the spirit of this joint approach is applicable to almost all stages of biological growth and development. I am currently applying my skills to the question of what kinds of mechanical feedbacks and stress fields are at play during the embryonic development of the common fruit fly.

The Common Fruit Fly

The common fruit fly (Drosophila melanogaster) is the best understood organism, both genetically and embryologically, making it an ideal system for the kind of modeling that I do. My work primarily focuses on a genetically coded regional cellular motion called Ventral Furrow Formation (VFF), where a spontaneous generation of curvature buckles a strip of cells on the underside of the embryo inwards. Although genetically driven, VFF is inherently a mechanical process that requires the coordination of individual cellular shape changes.

Many cellular components and processes are shared across species. Understanding how cells of the fruit fly harmonize their activity sheds light on how the cells of all organisms might communicate via mechanical stress. Through an interdisciplinary collaboration with Dr. Jeffrey Thomas (experimental biologist), Dr. Guo-Jie Gao (computational mechanical engineer), and Dr. Jerzy Blawzdziewicz (theoretical physicist), we have developed two models that capture different mechanical aspects of VFF.

Our preliminary results provided the first evidence that the behavior of cells on the underside of the embryo is likely the result of mechanical feedback, and were published in a special edition issue of the Journal of Physics: Condensed Matter. The article was flagged by reviewers as being of significant importance to the community and selected to be the subject of a featured post on the journal's blog. I am currently working to expand our experiments to include embryo-wide stress fields and mechanical feedbacks by combining aspects of our models to create a comprehensive 3D model of the embryo.

Future Direction

The understanding of mechanical feedback during biological development is still fragmented; I intend to continue working to fill this knowledge gap. This will include continued work with my collaborators on the development and refinement of a 3D model of the fruit fly embryo; however, dynamic system modeling can be applied to a wide array of biological processes. I am also interested in exploring how leaf growth may be guided by mechanical stress and how cells around an incision coordinate wound healing efforts through mechanical feedback. To increase the impact of such studies, I seek out collaborations with experimental researchers who can provide high resolution imaging. Funding for such collaborative projects from NSF, NIH, and DOD are possible.

Publications

The mechanics of cephalic furrow formation in the Drosophila embryo

Redowan A. Niloy, Michael C. Holcomb, Jeffrey H. Thomas, Jerzy Blawzdziewicz
Biophysical Journal, 2023   |  Elsevier - Science Direct (full text available until October 12, 2023) or bioRxiv.org (pre-print full text).

A Markov chain Monte Carlo model of mechanical-feedback-driven progressive apical constrictions captures the fluctuating collective cell dynamics in the Drosophila embryo

Guo-Jie Jason Gao, Michael C. Holcomb, Jeffrey H. Thomas, Jerzy Blawzdziewicz
Frontiers in Physics, 28, 2022   |  Frontiers in Physics (full text).

Mechanical Feedback and Robustness of Apical Constrictions in Drosophila Embryo Ventral Furrow Formation

Michael C. Holcomb, Guo-Jie Jason Gao, Mahsa Servati, Dylan Schneider, Presley K. McNeely, Jeffrey H. Thomas, Jerzy Blawzdziewicz
PLOS Computational Biology, 17(7), 2021   |  PLOS Computational Biology (full text).

Enhanced flow rate by the convergence of Tetris particles when discharged from a hopper with an obstacle

Guo-Jie Jason Gao, Fu-Ling Yang, Michael C. Holcomb, Jerzy Blawzdziewicz
Physical Review E, 103(6), 2021  |  Physical Review E or arXiv.org (full text).

Coordination of Ventral Furrow Formation During Drosophila Gastrulation Through Mechanical Stress Feedback

Michael C. Holcomb
Ph.D. Dissertation, Texas Tech University, 2019  |  Texas Tech University DSpace Repository (full text).

Understanding the Local Flow Rate Peak of a Hopper Discharging Discs through an Obstacle Using a Tetris-like Model

Guo-Jie J. Gao, Jerzy Blawzdziewicz, Michael C. Holcomb, Shigenobu Ogata
Granular Matter, 21(25), 2019  |  SpringerLink or arXiv.org (full text).

Embryo as an active granular fluid: stress-coordinated cellular constriction chains

Guo-Jie Jason Gao, Michael C. Holcomb, Jeffrey H. Thomas, Jerzy Blawzdziewicz
J. Phys. Condens. Matter, 28(41), 2016  |  IOP Science or arXiv.org (full text).