A cartoon of a mechanically activated protein called FimH in front of an electron micrograph of a bacteria, on which FimH is expressed.

Our laboratory studies the mechanical regulation of adhesive proteins. Our work includes both basic science and translational work in engineered materials. We are particularly interested in adhesion proteins that experience mechanical forces from external sources such as fluid flow and from internal sources such as cytoskeletal tension between cellular adhesion sites. We study the interface between mechanics and chemistry to understand how these mechanical forces regulate molecular structure and function.

Much of our work has been on "catch bonds" that are activated rather than torn apart by tensile mechanical force. In particular, we study mechanical regulation of bacterial biofilms (important in infectious diseases) and of thrombosis (critical in both bleeding disorders and heart attacks and strokes). Finally, we are interested in engineering novel bio-inspired "smart" adhesives that can be regulated with mechanical force, for example for medical microrobotics.

Our Asylum atomic force microscope (silver and blue apparatus) is mounted on top of an inverted epifluorescence microscope for simultaneous force measurements and optical viewing.

We integrate computational and experimental tools to address these questions. Some lab members do solely experimental work or solely computational work, while others do both.

Molecular dynamics simulations and Rosetta protein structure prediction methods help us understand the effect of externally applied mechanical force on protein structure and dynamics at atomic resolution.

Using these computational tools, we design mutations in proteins, and then make the proteins using molecular biology tools.

We use atomic force microscopy and microfluidic devices to apply forces to single adhesive bonds or molecules as well as to cells, communities of cells, and adhesive materials.

Finally, we use meso-scale stochastic mechanics simulations that bridge the nanoscale molecular behavior with microscale cell or even macroscale adhesive behavior.

We hope to apply our knowledge of the mechanical properties of biological adhesion to engineer novel materials and to design therapeutic interventions.

1) TRANSLATIONAL ENGINEERING AND BIOMATERIALS: We are engineering bio-inspired smart adhesives that are mechanically regulated. These smart adhesives may be used for medical micro-robotics and drug delivery. We are working on translational applications of this research and welcome new collaborators.

2) INFECTION AND BIOFILMS: Biofilms are a major impediment to biomaterials. We are increasing understanding of how bacteria mechanically regulate their adhesion to form biofilms that allow them to resist antibiotics and immune responses. This understanding should lead to development of novel classes of antibiotics that inhibit the aggregation of bacteria into functional communities and leave them vulnerable to other means of eradication.

3) CARDIOVASCULAR RESEARCH: We are also getting a better understanding of how high fluid flow activates platelet adhesion and aggregation. This high shear mechanism of thrombosis can stop bleeding in injured arteries but can also completely block an artery that is narrowed due to atherosclerosis, and thus cause a heart attack or stroke. We hope that by understanding how mechanical force induces thrombosis, we can specifically prevent heart attacks and strokes with minimal risk of bleeding disorders.

ENGINEERED BIOMATERIALS: We design novel biomaterials in the form of adhesive coatings that are reversible and nonfouling. We also study two major issues for biomaterial implants: bacterial infection and biofilms and thrombosis. Prof. Thomas is associated with UWEB.

MOLECULAR BIOENGINEERING AND NANOTECHNOLOGY: We use a variety of nanotechnology tools to learn how proteins are regulated by mechanical force. We then design or redesign proteins that are mechanically regulated, and learn how to integrate these into nanostructured adhesives with novel adhesive properties. Prof. Thomas is a member of the UW Center for Nanotechnology and the UW Molecular Biophysics Training Grant.

COMPUTATIONAL AND INTEGRATIVE BIOENGINEERING: We use (and develop in collaboration with David Baker) computational tools for dynamic protein structure analysis . We also develop our own meso-scale simulation tools for understanding cellular adhesive processes and for designing nanostructured adhesives.