- Post Doctoral
MIT Unit Affiliation:
- Materials Science and Engineering
Post Doc Sponsor / Advisor:
Date PhD Completed:
Top 3 Areas of Expertise:
Expected End Date of Post Doctoral Position:
- Untangling the heterogeneity within adult stem cell populations through long-term in vitro imaging experiments to understand current therapeutic limitations and develop new technologies
- Utilizing a variety of experimental and computational techniques to probe the multiscale mechanical characteristics of cells
- Leading a team developing novel high-throughput assays to observe and mitigate microbe-influenced corrosion of steels
Escherichia coli thrive in aqueous environments and depend highly on their ability to adhere to tissue surfaces even in the presence of dislodging forces. Their adhesive ability is of interest not only because E. coli can often cause harmful infections, but also because their adhesive prowess is unmatched by artificial systems. E. coli exhibit a shear enhanced adhesion in which increased shearing forces actually improve their ability to bind to surfaces. E. coli express an adhesive protein called FimH that binds to mannosylated residues on tissue surfaces in a force dependent manner known as a catch bond. The FimH adhesins are displayed on the distal tips of adhesive appendages called fimbriae which can extend by uncoiling under tensile forces. In this thesis, I sought to achieve a better understanding of how the interplay between the FimH/mannose bond and fimbrial properties allows E. coli to accomplish their remarkable adhesive feats. I also tested whether these adhesive components could be removed from E. coli and used to mediate adhesion between engineered surfaces at larger scales. I developed a simulation system capable of testing hypotheses about E. coli’s adhesion and used it in conjunction with parallel-plate flow chamber and atomic force spectroscopy techniques to perform the work in this thesis. I found that a combination of fimbrial deformation and catch bond formation could explain the initiation of adhesion and that fimbrial uncoiling could explain the ability of E. coli to remain adhered when faced with changing shearing forces. Finally, I demonstrated the ability for FimH tethered by fimbriae to mediate adhesion between micron2 scale surfaces. The adhesion was both reversible and self-cleaning, resisting fouling by soluble inhibitors. Future work will attempt to continue scaling the adhesive to larger surfaces.
Top 5 Awards and honors (name of award, date received):
5 Recent Papers:
MJ Whitfield, T Ghose, WE Thomas. (2010), "Shear-Stabilized Rolling Behavior of E. coli Examined with Simulations," Biophysical Journal 99 (8), 2470-2478. http://www.sciencedirect.com/science/article/pii/S0006349510010404
MJ Whitfield, WE Thomas. (2011), "A Nanoadhesive Composed of Receptor-Ligand Bonds,"
The Journal of Adhesion 87 (5), 427-446. http://www.tandfonline.com/doi/abs/10.1080/00218464.2011.575311#.Ul2Ff8bkuTM
RK Paradise, MJ Whitfield, DA Lauffenburger, KJ Van Vliet. (2013), "Directional cell migration in an extracellular pH gradient: A model study with an engineered cell line and primary microvascular endothelial cells," Experimental Cell Research 319 (4), 487–497. http://www.sciencedirect.com/science/article/pii/S0014482712004521
MJ Whitfield, WCJ Lee, KJ Van Vliet. (2013), "Onset of heterogeneity in culture-expanded bone marrow stromal cells," Stem Cell Research 11 (3), 1365 - 1377. http://www.sciencedirect.com/science/article/pii/S187350611300130X
KH Li, MJ Whitfield, and KJ Van Vliet. (2013) “Beating the bugs: Roles of microbial biofilms in corrosion,” Corrosion Reviews, (in press).