Clifford P. Brangwynne
Engineering Quad, A313
Lab (609) 258-8222
Mary beth friedfeld
We are interested in understanding the physical principles underlying self-assembly of biological materials, including the cytoskeleton, sub-cellular organelles, cells, and tissues. Our research combines the tools of soft matter physics and molecular cell biology to understand the way in which the properties of biological materials play a role in fundamental biological processes, in particular embryonic development. To address these questions we work with the worm C. elegans, as well as the frog X. Laevis. We aim to ultimately use the understanding gained in these model organisms to develop self-assembling biomaterials for medical applications.
Patterning in Developing Embryos
Tissue patterning in early development is facilitated in part by asymmetric cell divisions, where a cell divides into two daughter cells that may be different in size, contain different molecular components, and ultimately give rise to different tissues in the adult organism. In C. elegans asymmetric divisions establish germ cells that will go on to form the reproductive gonad in the adult organism. As with many organisms, C. elegans germ cells contain RNA and protein rich germ granules ("P-granules") that are thought to play a role in keeping the germ cells in an un-differentiated stem-cell like state. P-granules localize within the cell cytoplasm in a complex process that relies on the formation of intracellular morphogen gradients that control P-granule assembly. The biophysical nature of these gradients, and the mechanism by which they control P granule stability, are still poorly understood.
Physical Properties and Function of RNA/Protein Bodies
Unlike conventional sub-cellular compartments such as vesicles, cells contain many compartments that form in the absence of membranes. These typically consist of assemblies of RNA and proteins, and include many cytoplasmic bodies such as P-granules. There are also many similar bodies within the nucleus, including Cajal bodies and nucleoli. We are interested in how these bodies form, how they carry out their biological functions, and the role their biophysical properties play. Together with the powerful genetics possible in the worm C. elegans, we also work with the large eggs of the frog X. Laevis.
Architecture and Dynamics of the Cytoskeleton
The cytoskeleton is a dynamic network of biopolymer filaments that plays a central role in many fundamental biological processes, including cell migration, cell division, and intracellular transport. We are interested in collective properties of the cytoskeleton, and the way in which these collective properties can function to spatially organize the cytoplasm of developing cells.
Zhu L, Brangwynne CP. (2015) Nuclear bodies: the emerging biophysics of nucleoplasmic phases. 34: 23-30. [Epub ahead of print]
Elbaum-Garfinkle S, Kim Y, ... Eckmann CR, Myong S, Brangwynne CP. (2015) The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics. 112: 7189-94. Pubmed
Gilpin W, Uppaluri S, Brangwynne CP. (2015) Worms under pressure: Bulk mechanical properties of C. elegans are independent of the cuticle. Biophys J. 108:1887-98. Pubmed
Weber SC, Brangwynne CP. (2015) Inverse size scaling of the nucleolus by a concentration-dependent phase transition. Curr Biol. 25:641-6. Pubmed
Brangwynne CP. (2013) Phase transitions and size scaling of membrane-less organelles. J Cell Biol. 203: 875-81. Pubmed
Feric M, Brangwynne CP. (2013) A nuclear F-actin scaffold stabilizes ribonucleoprotein droplets against gravity in large cells. Nat Cell Biol. 15: 1253-59. Pubmed
Broedersz CP, Brangwynne CP. (2013) Nuclear mechanics: Lamin webs and pathological blebs. Nucleus. 4: 156-59. Pubmed
Brangwynne CP, Johnson TL. (2013) The micro and macro of RNA function. Mol Biol Cell. 24: 679. Pubmed
Weber SC, Brangwynne CP. (2012) Getting RNA and protein in phase. Cell. 149: 1188-91. Pubmed
Brangwynne CP, Eckmann CR, Courson DS,...Hyman AA. (2009) Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science. 324: 1729-32. Pubmed
Greenan G, Brangwynne CP, Jaensch S, Gharakhani J, Jülicher F, Hyman AA. (2010) Centrosome size sets mitotic spindle length in Caenorhabditis elegans embryos. Curr Biol. 20: 353-58. Pubmed
Brangwynne CP, Koenderink GH, MacKintosh FC, Weitz DA. (2008) Cytoplasmic diffusion: molecular motors mix it up. J Cell Biol. 183: 583-87. PubMed
Brangwynne CP, Koenderink GH, MacKintosh FC, Weitz DA. (2008) Nonequilibrium microtubule fluctuations in a model cytoskeleton. Phys Rev Lett. 100: 118104. PubMed
Brangwynne CP, MacKintosh FC, Weitz DA. (2007) Force fluctuations and polymerization dynamics of intracellular microtubules. Proc Natl Acad Sci. 104: 16128-33. Pubmed
Brangwynne CP, Koenderink GH, Barry E, Dogic Z, MacKintosh FC, Weitz DA. (2007) Bending dynamics of fluctuating biopolymers probed by automated high-resolution filament tracking. Biophys J. 93: 346-59. Pubmed
Brangwynne CP, MacKintosh FC, Kumar S,...Weitz DA. (2006) Microtubules can bear enhanced compressive loads in living cells because of lateral reinforcement. J Cell Biol. 173: 733-41. Pubmed
Huang S, Brangwynne CP, Parker KK, Ingber DE. (2005) Symmetry-breaking in mammalian cell cohort migration during tissue pattern formation: Role of random-walk persistence. Cell Motil Cytoskeleton. 61: 201-13. Pubmed