@article{baldwin_haugh_2023, title={Semi-autonomous wound invasion via matrix-deposited, haptotactic cues}, volume={568}, ISSN={["1095-8541"]}, DOI={10.1016/j.jtbi.2023.111506}, abstractNote={Proper wound healing relies on invasion of fibroblasts via directed migration. While the related experimental and mathematical modeling literature has mainly focused on cell migration directed by soluble cues (chemotaxis), there is ample evidence that fibroblast migration is also directed by insoluble, matrix-bound cues (haptotaxis). Furthermore, numerous studies indicate that fibronectin (FN), a haptotactic ligand for fibroblasts, is present and dynamic in the provisional matrix throughout the proliferative phase of wound healing. In the present work, we show the plausibility of a hypothesis that fibroblasts themselves form and maintain haptotactic gradients in a semi-autonomous fashion. As a precursor to this, we examine the positive control scenario where FN is pre-deposited in the wound matrix, and fibroblasts maintain haptotaxis by removing FN at an appropriate rate. After developing conceptual and quantitative understanding of this scenario, we consider two cases in which fibroblasts activate the latent form of a matrix-loaded cytokine, TGFβ, which upregulates the fibroblasts' own secretion of FN. In the first of these, the latent cytokine is pre-patterned and released by the fibroblasts. In the second, fibroblasts in the wound produce the latent TGFβ, with the presence of the wound providing the only instruction. In all cases, wound invasion is more effective than a negative control model with haptotaxis disabled; however, there is a trade-off between the degree of fibroblast autonomy and the rate of invasion.}, journal={JOURNAL OF THEORETICAL BIOLOGY}, author={Baldwin, Scott A. and Haugh, Jason M.}, year={2023}, month={Jul} }
 @article{baldwin_van bruggen_koelbl_appalabhotla_bear_haugh_2021, title={Microfluidic devices fitted with "flowver" paper pumps generate steady, tunable gradients for extended observation of chemotactic cell migration}, volume={15}, ISSN={["1932-1058"]}, DOI={10.1063/5.0054764}, abstractNote={Microfluidics approaches have gained popularity in the field of directed cell migration, enabling control of the extracellular environment and integration with live-cell microscopy; however, technical hurdles remain. Among the challenges are the stability and predictability of the environment, which are especially critical for the observation of fibroblasts and other slow-moving cells. Such experiments require several hours and are typically plagued by the introduction of bubbles and other disturbances that naturally arise in standard microfluidics protocols. Here, we report on the development of a passive pumping strategy, driven by the high capillary pressure and evaporative capacity of paper, and its application to study fibroblast chemotaxis. The paper pumps—flowvers (flow + clover)—are inexpensive, compact, and scalable, and they allow nearly bubble-free operation, with a predictable volumetric flow rate on the order of μl/min, for several hours. To demonstrate the utility of this approach, we combined the flowver pumping strategy with a Y-junction microfluidic device to generate a chemoattractant gradient landscape that is both stable (6+ h) and predictable (by finite-element modeling calculations). Integrated with fluorescence microscopy, we were able to recapitulate previous, live-cell imaging studies of fibroblast chemotaxis to platelet derived growth factor (PDGF), with an order-of-magnitude gain in throughput. The increased throughput of single-cell analysis allowed us to more precisely define PDGF gradient conditions conducive for chemotaxis; we were also able to interpret how the orientation of signaling through the phosphoinositide 3-kinase pathway affects the cells’ sensing of and response to conducive gradients.}, number={4}, journal={BIOMICROFLUIDICS}, author={Baldwin, Scott A. and Van Bruggen, Shawn M. and Koelbl, Joseph M. and Appalabhotla, Ravikanth and Bear, James E. and Haugh, Jason M.}, year={2021}, month={Jul} }