Microscale Bio-Fluid Dynamics Research
The flow of fluid within blood vessels, across vessel walls, and through interstitial spaces within tissues is an essential mechanism for the transport of oxygen, nutrients, and paracrine signals through the body. Disruption of physiological flow is associated with atherosclerosis, ischemia, cancer, and several other pathologies. Cells have established mechanisms for sensing and responding to fluid flow, but it has been difficult to experimentally manipulate the complex, three-dimensional flow fields present in vivo to study their effect on cell response. The primary aim of my research program is to interrogate the role of these complex fluid flows in the development and progression of cardiovascular disease, and use my findings to develop novel treatments for these diseases. Microfluidic technology can recreate several key elements of the in vivo environment including unsteady, three-dimensional flow patterns. Combined with computational modeling of the fluid dynamics, these tools can be used to study the response of both individual cells and multicellular units to several modes of fluid flow. Specifically, I focus on the altered flow regimes that are characteristic of pathologies including fibrosis, cancer, and inflammation.
1) Galie PA, van Oosten A, Chen CS, Janmey PA. Application of multiple levels of shear stress to endothelial cells plated on polyacrylamide gels . Lab-on-a-Chip 2015; In press
2) Galie PA, Byfield FJ, Chen CS, Kresh JY, Janmey PA. Mechanically-stimulated contraction of engineered cardiac constructs using a microcantilever. IEEE TBME 2014; 62(2):438-442.
3) Galie PA, Nguyen DH, Choi CK, Cohen DM, Janmey PA, Chen CS. Fluid shear stress threshold regulates angiogenic sprouting. Proc Natl Acad Sci U S A. 2014; 111(22):7968-7973.
4) Galie PA, Stegemann JP. Injection of mesenchymal stromal cells into a mechanically stimulated in vitro model of cardiac fibrosis has paracrine effects on resident fibroblasts. Cytotherapy 2014; 16(7): 906-914.
5) Chopra A, Murray ME, Byfield FJ, Mendez MG, Halleluyan R, Restle DJ, Raz-Ben Aroush D, Galie PA, Pogoda K, Bucki R, Marcinkiewicz C, Prestwich GD, Zarembinski RI, Chen CS, Pure E, Kresh JY, Janmey PA. Augmentation of integrin-mediated mechanotransduction by hyaluronic acid. Biomaterials 2014; 35(1):71-82.
6) Nguyen DH, Stapleton SC, Yang MT, Cha SS, Choi CK, Galie PA, Chen CS. Biomimetic model to reconstitute angiogenic sprouting morphogenesis in vitro. Proc Natl Acad Sci U S A. 2013; 110(17):6712-7.
7) Miller JS, Stevens KR, Yang MT, Baker BM, Nguyen DH, Cohen DM, Toro E, Chen AA, Galie PA, Yu X, Chaturvedi R, Bhatia SN, Chen CS. Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat Mater. 2012 Sep;11(9):768-74.
8) Vaughan B, Galie PA, Zamankhan P, Stegemann JP, Grotberg J. Solute transport in a cyclically deforming poroelastic medium. Biophysical Journal 2013;105(9):2188-2198.
9) Galie PA, Khalid N, Carnahan K, Westfall MV, Stegemann JP. Substrate stiffness affects sarcomere and costamere structure and electrophysiological function of isolated adult cardiomyocytes. Cardiovascular Pathology 2012; 22(3):219-227.
10) Galie PA, Russell MW, Westfall MV, Stegemann JP. Interstitial fluid flow and cyclic strain differentially regulate cardiac fibroblast activation via AT1R and TGF-β. Exp Cell Res 2012; 318(1):75-84.
11) Galie PA, Spilker RL, Stegemann JP. A linear, biphasic model incorporating a Brinkman term to describe the mechanics of cell-seeded collagen hydrogels. Ann Biomed Eng 2011;39(11):2767-79.
12) Galie PA, Stegemann JP, Simultaneous interstitial fluid flow and cyclic strain in a PDMS bioreactor. Tissue Eng Part C 2011;17(5):527-36.
13) Galie PA, Westfall MV, Stegemann JP. Reduced serum content and increased matrix stiffness promote the cardiac myofibroblast transition in 3D collagen matrices. Cardiovascular Pathology 2011;20(6):325-33.
14) Galie P, Spilker RL. A two-dimensional computational model of lymph transport across primary lymphatic valves, J Biomech Eng 2009;31(11):111004-1:9.
In the News:
IEEE Transactions on Biomedical Engineering
Mechanically-stimulated contraction of engineered cardiac constructs using a microcantilever
Boston University News & Events
New Study Probes Mechanics of Blood Vessel Formation
Reconstituting Angiogenesis in Vitro
Department of Physiology
University of Pennsylvania
1010 Vagelos Laboratories
3340 Smith Walk