Dr. Ilya Levental

Though the structure-function relationship of polypeptides is one of the core dogmas of molecular cell biology, the functional aspects of lipid structure have been little explored. The existence of lipid rafts, i.e. lateral membrane domains arising from preferential interactions between specific lipids, suggests that such structure could be an important contributor to cell function and pathophysiology. The involvement of these domains in diverse cellular functions (e.g. growth factor signaling and membrane trafficking) and disease processes - including cancer, autoimmunity, and Alzheimer’s disease - has confirmed this potential and energized the field. Recent compelling evidence has definitively resolved the controversy about the existence of membrane domains; however, the mechanisms by which they regulate cell function remain speculative due to a lack of quantitative, robust tools for their investigation.

 Our primary research goals are: (1) to investigate the physical principles behind the formation of membrane domains; (2) to uncover the mechanisms by which these domains regulate cell signaling; and (3) to develop strategies to modulate these mechanisms for treatment of human disease. 

Ongoing project #1: using an exciting and novel tool in membrane biology, phase separation in Giant Plasma Membrane Vesicles (GPMVs) to assay raft-dependent ligand binding and oligomerization of the Epidermal Growth Factor Receptor (EGFR) and its oncogenic homolog HER2.

Ongoing project #2: measuring changes in raft formation, physical properties, and composition of plasma membranes of mesenchymal stem cells as they proceed through terminal differentiation

Ongoing project #3: developing a quantitative protein lipidation assay and using it to characterize palmitoylation dynamics in immune and cancer cell signaling

Ongoing project #4: designing transmembrane domain mutants of EGFR to determine the requirements for its raft association and oligomer formation

Ongoing project #5: developing drugs to specifically target protein transmembrane domains

Selected Publications

Raft domains of various properties and compositions in plasma membrane vesicles. Ilya Levental, M Grzybek, K Simons. PNAS USA 2012

Palmitoylation regulates raft affinity for the majority of integral raft proteins. Ilya Levental, D Lingwood, M Grzybek, U Coskun, K Simons. PNAS 2010

Greasing their way:  lipid modifications determine protein association with membrane rafts. Ilya Levental, M Grzybek, K Simons. Biochemistry    2010

A simple indentation device for measuring micrometer-scale tissue stiffness. Ilya Levental*, KR Levental*, EA Klein, RK Assoian, RT Miller, RG Wells, PA Janmey. Journal of Physics: Condensed Matter    2010              *authors contributed equally

Matrix crosslinking forces tumor progression by enhancing integrin signaling. 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. Cell 2009 

Cholesterol-dependent phase separation in cell-derived giant plasma-membrane vesicles. Ilya Levental, FJ Byfield, P Chowdhury, F Gai, T Baumgart, PA Janmey. Biochemical Journal 2009   

Calcium-Dependent Lateral Organization in Phosphatidylinositol 4,5-Bisphosphate (PIP2)- and Cholesterol-Containing Monolayers. Ilya Levental*, DA Christian*, YH Wang, JJ Madara, DE Discher, PA Janmey. Biochemistry 2009    *authors contributed equally

Fibroblast adaptation and stiffness matching to soft elastic substrates. J Solon*, Ilya Levental*, K Sengupta, PA Georges, PA Janmey. Biophysical Journal  2007  *authors contributed equally

Soft biological materials and their impact on cell function. Ilya Levental, PC Georges, PA Janmey. Soft Matter  2007

Additional Publications

Program Affiliation:

Program in Cell and Regulatory Biology

Lab web site