@article{ahmed_yang_ozcam_efimenko_weiger_genzer_haugh_2011, title={Poly(vinylmethylsiloxane) Elastomer Networks as Functional Materials for Cell Adhesion and Migration Studies}, volume={12}, ISSN={["1526-4602"]}, DOI={10.1021/bm101549y}, abstractNote={Cell migration is central to physiological responses to injury and infection and in the design of biomaterial implants. The ability to tune the properties of adhesive materials and relate those properties in a quantitative way to the dynamics of intracellular processes remains a definite challenge in the manipulation of cell migration. Here, we propose the use of poly(vinylmethylsiloxane) (PVMS) networks as novel substrata for cell adhesion and migration. These materials offer the ability to tune independently chemical functionality and elastic modulus. Importantly, PVMS networks are compatible with total internal reflection fluorescence (TIRF) microscopy, which is ideal for interrogating the cell-substratum interface; this latter characteristic presents a distinct advantage over polyacrylamide gels and other materials that swell with water. To demonstrate these capabilities, adhesive peptides containing the arginyl-glycyl-aspartic acid (RGD) tripeptide motif were successfully grafted to the surface of PVMS network using a carboxyl-terminated thiol as a linker. Peptide-specific adhesion, spreading, and random migration of NIH 3T3 mouse fibroblasts were characterized. These experiments show that a peptide containing the synergy sequence of fibronectin (PHSRN) in addition to RGD promotes more productive cell migration without markedly enhancing cell adhesion strength. Using TIRF microscopy, the dynamics of signal transduction through the phosphoinositide 3-kinase pathway were monitored in cells as they migrated on peptide-grafted PVMS surfaces. This approach offers a promising avenue for studies of directed migration and mechanotransduction at the level of intracellular processes.}, number={4}, journal={BIOMACROMOLECULES}, publisher={American Chemical Society (ACS)}, author={Ahmed, Shoeb and Yang, Hyun-kwan and Ozcam, Ali E. and Efimenko, Kirill and Weiger, Michael C. and Genzer, Jan and Haugh, Jason M.}, year={2011}, month={Apr}, pages={1265–1271} }
 @article{weiger_ahmed_welf_haugh_2010, title={Directional Persistence of Cell Migration Coincides with Stability of Asymmetric Intracellular Signaling}, volume={98}, ISSN={["1542-0086"]}, DOI={10.1016/j.bpj.2009.09.051}, abstractNote={It has long been appreciated that spatiotemporal dynamics of cell migration are under the control of intracellular signaling pathways, which are mediated by adhesion receptors and other transducers of extracellular cues. Further, there is ample evidence that aspects of cell migration are stochastic: how else could it exhibit directional persistence over timescales much longer than typical signal transduction processes, punctuated by abrupt changes in direction? Yet the mechanisms by which signaling processes affect those behaviors remain unclear. We have developed analytical methods for relating parallel live-cell microscopy measurements of cell migration dynamics to the intracellular signaling processes that govern them. In this analysis of phosphoinositide 3-kinase signaling in randomly migrating fibroblasts, we observe that hot spots of intense signaling coincide with localized cell protrusion and endure with characteristic lifetimes that correspond to those of cell migration persistence. We further show that distant hot spots are dynamically and stochastically coupled. These results are indicative of a mechanism by which changes in a cell's direction of migration are determined by a fragile balance of relatively rapid intracellular signaling processes.}, number={1}, journal={BIOPHYSICAL JOURNAL}, publisher={Elsevier BV}, author={Weiger, Michael C. and Ahmed, Shoeb and Welf, Erik S. and Haugh, Jason M.}, year={2010}, month={Jan}, pages={67–75} }
 @article{weiger_wang_krajcovic_melvin_rhoden_haugh_2009, title={Spontaneous phosphoinositide 3-kinase signaling dynamics drive spreading and random migration of fibroblasts}, volume={122}, ISSN={["1477-9137"]}, DOI={10.1242/jcs.037564}, abstractNote={During directed cell migration (chemotaxis), cytoskeletal dynamics are stimulated and spatially biased by phosphoinositide 3-kinase (PI3K) and other signal transduction pathways. Live-cell imaging using total internal reflection fluorescence (TIRF) microscopy revealed that, in the absence of soluble cues, 3′-phosphoinositides are enriched in a localized and dynamic fashion during active spreading and random migration of mouse fibroblasts on adhesive surfaces. Surprisingly, we found that PI3K activation is uncoupled from classical integrin-mediated pathways and feedback from the actin cytoskeleton. Inhibiting PI3K significantly impairs cell motility, both in the context of normal spreading and when microtubules are dissociated, which induces a dynamic protrusion phenotype as seen by TIRF in our cells. Accordingly, during random migration, 3′-phosphoinositides are frequently localized to regions of membrane protrusion and correlate quantitatively with the direction and persistence of cell movement. These results underscore the importance of localized PI3K signaling not only in chemotaxis but also in basal motility/migration of fibroblasts.}, number={3}, journal={JOURNAL OF CELL SCIENCE}, publisher={The Company of Biologists}, author={Weiger, Michael C. and Wang, Chun-Chao and Krajcovic, Matej and Melvin, Adam T. and Rhoden, John J. and Haugh, Jason M.}, year={2009}, month={Feb}, pages={313–323} }