Kandice Levental

Associate Professor of Research, Molecular Physiology and Biological Physics

Primary Location

1340 Jefferson Park Ave
Pinn Hall 4010
Charlottesville, VA 22903

Website

Bio & Overview

The structure and composition 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. Finally, the majority of cellular lipids are derived directly from dietary sources, but how a cell is able to buffer dietary changes and maintain homeostasis is unclear. Combining tools from molecular and cell biology, membrane biophysics, protein biochemistry, and synthetic biology we seek to answer fundamental questions about the nature and function of cellular lipid membranes.

Academic Information

Department: Molecular Physiology and Biological Physics

Primary Education

BS, Chemical Engineering, University of Texasnull
PhD, Bioengineering, University of Pennsylvanianull

Other Appointments

Associated Professor of Research, Molecular Physiology and Biological Physics

Other Affiliations

BIMS
Experimental Pathology and Laboratory Medicine

Research Interests

Fundamental mechanisms by which membranes and dietary lipids regulate cell physiology

Research Disciplines

Molecular Physiology and Biological Physics

Research Opportunities

Biophysics & Structural Biology
Cell Biology
Chemistry and Physics of Living Systems
Physiological Basis of Human Disease

Selected Publications

2024

Castello-Serrano, I., Heberle, F. A., Diaz-Rohrer, B., Ippolito, R., Shurer, C. R., Lujan, P., . . . Levental, I. (2024). Partitioning to ordered membrane domains regulates the kinetics of secretory traffic. ELIFE, 12. doi:10.7554/eLife.89306

Levental, K. R., & Henry, W. S. (2024). Lipidomes define immune cell identity. NATURE CELL BIOLOGY, 26(4), 516-518. doi:10.1038/s41556-024-01398-8

Shurer, C. R., & Levental, K. R. (2024). Membranes get in shape: Biophysics of curving bilayers.. Biophysical journal, 123(3), 273-276. doi:10.1016/j.bpj.2024.01.004

Wang, H. -Y., Dey, S., & Levental, K. R. (2024). Applications of phase-separating multi-bilayers in protein-membrane domain interactions.. Methods in enzymology, 700, 275-294. doi:10.1016/bs.mie.2024.04.024

2023

Wang, H. -Y., Chan, S. H., Dey, S., Castello-Serrano, I., Rosen, M. K., Ditlev, J. A., . . . Levental, I. (2023). Coupling of protein condensates to ordered lipid domains determines functional membrane organization. SCIENCE ADVANCES, 9(17). doi:10.1126/sciadv.adf6205

Ward, A. E., Sokovikova, D., Waxham, M. N., Heberle, F. A., Levental, I., Levental, K. R., . . . Tamm, L. K. (2023). Serinc5 Restricts HIV Membrane Fusion by Altering Lipid Order and Heterogeneity in the Viral Membrane. ACS INFECTIOUS DISEASES, 9(4), 773-784. doi:10.1021/acsinfecdis.2c00478

Diaz-Rohrer, B., Castello-Serrano, I., Chan, S. H., Wang, H. -Y., Shurer, C. R., Levental, K. R., & Levental, I. (2023). Rab3 mediates a pathway for endocytic sorting and plasma membrane recycling of ordered microdomains. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 120(10). doi:10.1073/pnas.2207461120

2022

Sych, T., Levental, K. R., & Sezgin, E. (2022). Lipid-Protein Interactions in Plasma Membrane Organization and Function. ANNUAL REVIEW OF BIOPHYSICS, 51, 135-156. doi:10.1146/annurev-biophys-090721-072718

2021

Matias, M. I., Yong, C. S., Foroushani, A., Goldsmith, C., Mongellaz, C., Sezgin, E., . . . Dardalhon, V. (2021). Regulatory T cell differentiation is controlled by αKG-induced alterations in mitochondrial metabolism and lipid homeostasis. CELL REPORTS, 37(5). doi:10.1016/j.celrep.2021.109911

Zinocker, M. K., Svendsen, K., Levental, K. R., Levental, I., & Dankel, S. N. (2021). The homeoviscous adaptation to dietary lipids (HADL) hypothesis is probably incorrect Reply. AMERICAN JOURNAL OF CLINICAL NUTRITION, 113(6), 1712-1713. doi:10.1093/ajcn/nqab111

Symons, J. L., Cho, K. -J., Chang, J. T., Du, G., Waxham, M. N., Hancock, J. F., . . . Levental, K. R. (2021). Lipidomic atlas of mammalian cell membranes reveals hierarchical variation induced by culture conditions, subcellular membranes, and cell lineages. SOFT MATTER, 17(2), 288-297. doi:10.1039/d0sm00404a

2020

Lorent, J. H., Levental, K. R., Ganesan, L., Rivera-Longsworth, G., Sezgin, E., Doktorova, M., . . . Levental, I. (2020). Author Correction: Plasma membranes are asymmetric in lipid unsaturation, packing and protein shape. NATURE CHEMICAL BIOLOGY, 16(6), 710. doi:10.1038/s41589-020-0540-y

Lorent, J. H., Levental, K. R., Ganesan, L., Rivera-Longsworth, G., Sezgin, E., Doktorova, M. D., . . . Levental, I. (2020). Plasma membranes are asymmetric in lipid unsaturation, packing and protein shape. NATURE CHEMICAL BIOLOGY, 16(6), 644-+. doi:10.1038/s41589-020-0529-6

Levental, K. R., Malmberg, E., Symons, J. L., Fan, Y. -Y., Chapkin, R. S., Ernst, R., & Levental, I. (2020). Lipidomic and biophysical homeostasis of mammalian membranes counteracts dietary lipid perturbations to maintain cellular fitness. NATURE COMMUNICATIONS, 11(1). doi:10.1038/s41467-020-15203-1

Skinkle, A. D., Levental, K. R., & Levental, I. (2020). Cell-Derived Plasma Membrane Vesicles Are Permeable to Hydrophilic Macromolecules. BIOPHYSICAL JOURNAL, 118(6), 1292-1300. doi:10.1016/j.bpj.2019.12.040

2018

Torres-Adorno, A. M., Vitrac, H., Qi, Y., Tans, L., Levental, K. R., Fan, Y. -Y., . . . Ueno, N. T. (2019). Eicosapentaenoic acid in combination with EPHA2 inhibition shows efficacy in preclinical models of triple-negative breast cancer by disrupting cellular cholesterol efflux. ONCOGENE, 38(12), 2135-2150. doi:10.1038/s41388-018-0569-5

Cornell, C. E., Skinkle, A. D., He, S., Leyental, I., Levental, K. R., & Keller, S. L. (2018). Tuning Length Scales of Small Domains in Cell-Derived Membranes and Synthetic Model Membranes. BIOPHYSICAL JOURNAL, 115(4), 690-701. doi:10.1016/j.bpj.2018.06.027

van der Hoeven, D., Cho, K. -J., Zhou, Y., Ma, X., Chen, W., Naji, A., . . . Hancock, J. F. (2018). Sphingomyelin Metabolism Is a Regulator of K-Ras Function. MOLECULAR AND CELLULAR BIOLOGY, 38(3). doi:10.1128/MCB.00373-17

2017

Levental, K. R., Surma, M. A., Skinkle, A. D., Lorent, J. H., Zhou, Y., Klose, C., . . . Levental, I. (2017). ω-3 polyunsaturated fatty acids direct differentiation of the membrane phenotype in mesenchymal stem cells to potentiate osteogenesis. SCIENCE ADVANCES, 3(11). doi:10.1126/sciadv.aao1193

Lorent, J. H., Diaz-Rohrer, B., Lin, X., Spring, K., Gorfe, A. A., Levental, K. R., & Levental, I. (2017). Structural determinants and functional consequences of protein affinity for membrane rafts. NATURE COMMUNICATIONS, 8. doi:10.1038/s41467-017-01328-3

He, J., Zhang, F., Tay, L. W. R., Boroda, S., Nian, W., Levental, K. R., . . . Du, G. (2017). Lipin-1 regulation of phospholipid synthesis maintains endoplasmic reticulum homeostasis and is critical for triple-negative breast cancer cell survival. FASEB JOURNAL, 31(7), 2893-2904. doi:10.1096/fj.201601353R

2016

Nowak, M., Freudenberg, U., Tsurkan, M. V., Werner, C., & Levental, K. R. (2017). Modular GAG-matrices to promote mammary epithelial morphogenesis in vitro. BIOMATERIALS, 112, 20-30. doi:10.1016/j.biomaterials.2016.10.007

Levental, K. R., Lorent, J. H., Lin, X., Skinkle, A. D., Surma, M. A., Stockenbojer, E. A., . . . Levental, I. (2016). Polyunsaturated Lipids Regulate Membrane Domain Stability by Tuning Membrane Order. BIOPHYSICAL JOURNAL, 110(8), 1800-1810. doi:10.1016/j.bpj.2016.03.012

2014

Diaz-Rohrer, B., Levental, K. R., & Levental, I. (2014). Rafting through traffic: Membrane domains in cellular logistics. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1838(12), 3003-3013. doi:10.1016/j.bbamem.2014.07.029

Diaz-Rohrer, B. B., Levental, K. R., Simons, K., & Levental, I. (2014). Membrane raft association is a determinant of plasma membrane localization. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(23), 8500-8505. doi:10.1073/pnas.1404582111

Mouw, J. K., Yui, Y., Damiano, L., Bainer, R. O., Lakins, J. N., Acerbi, I., . . . Weaver, V. M. (2014). Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression. NATURE MEDICINE, 20(4), 360-+. doi:10.1038/nm.3497

2013

Tsurkan, M. V., Chwalek, K., Prokoph, S., Zieris, A., Levental, K. R., Freudenberg, U., & Werner, C. (2013). Defined Polymer-Peptide Conjugates to Form Cell-Instructive starPEG-Heparin Matrices In Situ. ADVANCED MATERIALS, 25(18), 2606-2610. doi:10.1002/adma.201300691

2012

Prokoph, S., Chavakis, E., Levental, K. R., Zieris, A., Freudenberg, U., Dimmeler, S., & Werner, C. (2012). Sustained delivery of SDF-1α from heparin-based hydrogels to attract circulating pro-angiogenic cells. BIOMATERIALS, 33(19), 4792-4800. doi:10.1016/j.biomaterials.2012.03.039

Freudenberg, U., Sommer, J. -U., Levental, K. R., Welzel, P. B., Zieris, A., Chwalek, K., . . . Werner, C. (2012). Using Mean Field Theory to Guide Biofunctional Materials Design. ADVANCED FUNCTIONAL MATERIALS, 22(7), 1391-1398. doi:10.1002/adfm.201101868

2011

Chwalek, K., Levental, K. R., Tsurkan, M. V., Zieris, A., Freudenberg, U., & Werner, C. (2011). Two-tier hydrogel degradation to boost endothelial cell morphogenesis. BIOMATERIALS, 32(36), 9649-9657. doi:10.1016/j.biomaterials.2011.08.078

Zieris, A., Chwalek, K., Prokoph, S., Levental, K. R., Welzel, P. B., Freudenberg, U., & Werner, C. (2011). Dual independent delivery of pro-angiogenic growth factors from starPEG-heparin hydrogels. JOURNAL OF CONTROLLED RELEASE, 156(1), 28-36. doi:10.1016/j.jconrel.2011.06.042

2010

Tsurkan, M. V., Chwalek, K., Levental, K. R., Freudenberg, U., & Werner, C. (2010). Modular StarPEG-Heparin Gels with Bifunctional Peptide Linkers. MACROMOLECULAR RAPID COMMUNICATIONS, 31(17), 1529-1533. doi:10.1002/marc.201000155

Zieris, A., Prokoph, S., Levental, K. R., Welzel, P. B., 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, 31(31), 7985-7994. doi:10.1016/j.biomaterials.2010.07.021

Levental, I., Levental, K. R., Klein, E. A., Assoian, R., Miller, R. T., Wells, R. G., & Janmey, P. A. (2010). A simple indentation device for measuring micrometer-scale tissue stiffness. JOURNAL OF PHYSICS-CONDENSED MATTER, 22(19). doi:10.1088/0953-8984/22/19/194120