Education & Training
- Postdoctoral Fellow
- Leibniz Institute of Polymer Research Dresden, Germany 2012
- University of Pennsylvania, 2008
Areas of Interests
- Research Interest
- Differentiation of the Plasma Membrane
Differentiation of the Plasma Membrane
The structure of the plasma membrane is a major determinant of its function, and while recent advances in super-resolution microscopy and isolated mammalian plasma membranes have provided key insights into this relationship, major open questions remain. For example, the precise molecular mechanisms of functional regulation of signaling by membrane domains are unknown. Further, the diversity of plasma membrane structure and composition, and the impact of this diversity on those cells’ functions, in various cell lineages have not been widely explored.
Mesenchymal stem cells provide an excellent, well-controlled system to study changes in plasma membranes because they can be directed to undergo differentiation along several lineages within a short timeframe (~2 weeks) and with minimal biochemical perturbations. This capacity allows us to assay several distinct cell types (e.g. undifferentiated, adipocyte, osteocyte) from an original well-defined precursor population and grown with nearly identical conditions (i.e. medium, serum, etc).
To investigate plasma membrane structure and composition, we use a novel and exciting method for isolating Giant Plasma Membrane Vesicles that separate into coexisting liquid phases, representative of lipid raft domains in live cells. We find that both phase separation and overall membrane packing are significantly affected by differentiation, clearly showing that different cell types have different plasma membranes.
We are currently investigating:
- The compositional changes of both protein and lipid constituents of the differentiated plasma membranes.
- The relationship between plasma membrane composition and its physical properties.
- The functional consequences of plasma membrane differences in the terminally differentiated cell types.
- The feedback between plasma membrane differentiation and progression from multipotent stem cells to functional tissue cells.
- He J, Zhang F, Tay LW, Boroda S, Nian W, Levental KR, Levental I, Harris TE, Chang JT, Du G. (2017). Lipin-1
regulation of phospholipid synthesis maintains endoplasmic reticulum homeostasis and is critical for triple-negative breast cancer cell survival. FASEB J., Jul;31(7):2893-2904. doi: 10.1096/fj.201601353R. Epub 2017 Mar 27.
- Tsurkan MV, Chwalek K, Prokoph S, Zieris A, Levental KR*, Freudenberg U*, Werner C. (2013). Defined polymer-peptide conjugates to form cell-instructive starPEG-heparin matrices in situ. Advanced Materials, 25(18):2606-2610. (* corresponding authors)
- Prokoph S, Chavakis EM, Levental KR, Zieris A, Freudenberg U, Dimmeler S, Werner C. (2012). Sustained delivery of SDF-1alpha from heparin-based hydrogels to attract circulating pro-angiogenic cells. Biomaterials.
- Chwalek K, Levental KR, Tsurkan MV, Zieris A, Freudenberg U, Werner C. (2011). Two-tier hydrogel degradation to boost endothelial cell morphogenesis. Biomaterials.
- Zieris A, Chwalek K, Prokoph S, Levental KR, Welzel PB, Freudenberg U, Werner C. (2011). Dual independent delivery of pro-angiogenic growth factors from starPEG-heparin hydrogels. J Controlled Release.
- Tsurkan MV, Chwalek K, Levental KR, Freudenberg U, Werner C. (2010) Modular StarPEG-Heparin Gels with Bifunctional Peptide Linkers. Macromolecular Rapid Communications.
- Levental I*, Levental KR*, Klein EA, Assoian R, Miller RT, Wells RG, Janmey PA. (2010) A simple indentation technique for measuring micron-scale tissue stiffness heterogeneity. J Phys – Condensed Matter. *authors contributed equally
- Zieris A, Prokoph S, Levental KR, Welzel PB, Grimmer M, Freudenberg U, Werner C. (2010) FGF-2 and VEGF functionalization of starPEG-heparin hydrogels to modulate biomolecular and physical cues of angiogenesis. Biomaterials.
- Tsurkan MV, Levental KR, Freudenberg U, Werner C. (2010) Enzymatically degradable heparin-polyethylene glycol gels with controlled mechanical properties. Chem Communications.
- Zieris A, Prokoph S, Welzel PB, Grimmer M, Levental KR, Panyanuwat W, Freudenberg U, Werner C. (2010) Analytical approaches to uptake and release of hydrogel-associated FGF-2. J Materials Sci: Materials in Med.
- Levental KR*, Yu H*, Kass L, Lakins JN, Egeblad M, Erler JT, Fong SF, Csiszar K, Giaccia A, Weninger W, Yamauchi M, Gasser DL, Weaver VM. (2009) Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell. *authors contributed equally
- Paszek MJ, Zahir N, Johnson KR, Lakins JN, Rozenberg GI, Gefen A, Reinhart-King CA, Margulies SS, Dembo M, Boettiger D, Hammer DA, Weaver VM. (2005) Tensional homeostasis and the malignant phenotype. Cancer Cell.
- Johnson KR, Leight JL, Weaver VM. (2007) “Demystifying three-dimensional force and tissue morphogenesis.” Methods in Cell Biology: Cell Mechanics. Academic Press, San Diego.
- Christman KL, Fang Q, Yee MS, Johnson KR, Sievers RE, Lee RJ. (2005) Enhanced neovasculature formation in ischemic myocardium following delivery of pleiotrophin plasmid in a biopolymer. Biomaterials.