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Richard Dickinson - In our research, we apply engineering principles to study the behavior of living cells. That is, we use a combination of mathematical modeling, quantitative experimentation, together with the tools of molecular cell biology to better understand the relationship between cell function and the physical and molecular properties of cells and their surroundings. This understanding is relevant to several biotechnological, biomedical, biomaterial and pharmaceutical applications. This field is often called cellular bioengineering or cellular engineering.

One major area of focus is cell adhesion, which is relevant to applications such as the design of biomaterials for biomedical implants, cell carriers for bioreactors in the bioprocessing industry, and filters to remove microorganisms in water purification. Our goal is to develop models that can predict the probability and strength of adhesion as a function of measurable molecular and physical properties of the cell and substratum. In addition to “macroscopic” surface properties such as hydrophobicity and surface charge, we are interested in the role of specific interactions between cell surface molecules and the substratum. In this work, we have developed a novel force measurement instrument involving an optical trap force-transducer and evanescent wave light scattering to probe dynamic interaction forces between a single microbe and a surface with nanometer resolution and a sensitivity of tens of femptoNewtons (1 fN = 10-15 N) (Clapp and Dickinson. Langmuir. 17:2182-91. (2001)). Our technique has the force-distance profile between a single bacterium and a substratum.

Another major area of focus is cell migration, which is relevant to a number of physiological processes, such as wound healing, inflammation, and embryogenesis, as well as to pathological processes such as tumor cell metastasis. Cell migration is also involved in the proper function of bioartificial devices in tissue engineering applications, where cell infiltration or localization is essential. Our goal is again to develop predictive models relating the extent and direction of migration to the molecular and physical properties of the cell and the material through which it moves (e.g. Burgess, B. T. *, J. L. Myles, R. B. Dickinson Ann. Biomed. Eng. 28:110-118. (2000)). The ultimate goal of these models is to provide as basis for the rational design the spatial gradients of molecular “cues” to direct the migration cells in engineered tissues.

We also study the intracellular mechanisms of actin-based motility using a combination of biophysical modeling, our picoNewton-scale force-measurement techniques, and molecular cell biology. In collaboration with faculty in the College of Medicine, we are investigating the molecular motor responsible for force generation by actin polymerization at a surface. This force results in cell protrusions during cell crawling as well as the intracellular transport of vesicles and some invasive pathogenic microorganisms such as Listeria monocytogenes.