Research Interests

Molecular-to-cellular bioengineering/biomechanics: Towards a quantitative understanding of mechano-sensing, -signaling, and -regulation

Minuscule mechanical forces, though often overlooked, play a vital role in many molecular-to-cellular processes. Prominent examples include the interaction between adhesive biomolecules that glue cells together to form tissues, and the active deformation of a white blood cell engulfing its (e.g., an opsonized bacterium). Likewise, a bioengineered drug-delivery capsule inevitably encounters a number of mechanical dilemmas in its transport and attachment to a target and during the controlled release of its content.

Examples of nano-to-micro-mechanical experiments. (a) A biomembrane force probe is used to test the adhesion strength between P-selectin and a neutrophil. (b) A combination of optical tweezers and micropipette manipulation is used to study DNA elasticity. (c) A paramagnetic bead is manipulated using a magnetic puller as it drags along a lipid vesicle, extruding a membrane tether. (d) A human neutrophil attempts to a large, antibody-covered bead (â??frustrated phagocytosis).

Phagocytosis of beads of different sizes: Comparison of experiment (top) and computer simulation (bottom).

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Our multiscale approach uses the tools of mechanics and high-resolution optical microscopy to deepen the understanding of how nature does things in the nanoworld and where pathogens may attack our natural defenses. On the smallest scale, we characterize isolated single-molecule interactions using custom-developed, ultrasensitive force probes. In vivo these biomolecules are often supported by soft subcellular structures like membranes or the cytoskeleton. The dynamical properties of such structures crucially affect the way in which the interacting molecules experience force. A more complete picture of biologically relevant nano-to-microscale processes, therefore, requires a sound knowledge of the mechanics of membranes and whole cells. Combining our force probes with advanced micropipette aspiration and micromanipulation allows us to study with exceptional resolution the elasticity and cohesive strength of artificial and biological membranes. Similar experimental setups are used to establish and characterize the mechanical determinants of cellular processes like leukocyte adhesion and phagocytosis and how they are affected by disease.

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