Molecular & Cellular Biophysics

Over the last few decades, structural biologists have delivered a treasure-trove of data on the shapes and sizes of large biomacromolecules and their assemblies. When this information is combined with the biochemistry and genetics to understand aspects of the kinetics and manipulate them, we can begin to ask questions about how structure impacts function dynamically at both the level of the individual molecule and in large aggregates of molecules such as polymeric filaments and membranes.

We are particularly interested in the statistical and continuum mechanics of macromolecular assemblies such as disordered cytoskeletal-like networks of actin and crosslinkers, ordered assemblies such as microtubules, actin bundles, DNA-loops etc. in the context of questions such as the linear and nonlinear rheology of these “living” materials”, the kinetics of growth and shrinkage, and the mechanochemistry of active biological engines driven by growth, shrinkage and spring-like behavior.

Recently, we have also become interested in how we might control the formation and dissolution of  protein and liquid aggregates in the context of amyloid diseases, liquid-liquid phase separation, bringing in ideas from deterministic, stochastic, feedback and feedforward control theory to study these questions.

Related Publications

Mechanics and kinetics of dynamic instability. T.C.T. Michaels, S. Feng, H. Liang, and L Mahadevan, eLife (2020) 9:e54077. [DOI] [View PDF] [Download PDF]
Non-equilibration of hydrostatic pressure in blebbing cells, G. Charras, J. Yarrow, M. Horton, L. Mahadevan and T. Mitchison,  Nature , 435, 365-69. 2005. [View PDF] [Download PDF]
Mechanical basis for fibrillar bundle morphology. T. Michaels, E. Memet, and L. Mahadevan, Soft Matter (2020), 16, 9306-18. [ONLINE ARTICLE] [DOI] [View PDF] [Download PDF]
Motility driven by macromolecular springs and ratchets, Mahadevan, L. and P. Matsudaira,  Science , 288, 95-99, 2000. [View PDF] [Download PDF]
The force-velocity relationship for the actin-based motility of Listeria-Monocytogenes, McGrath, J., J. Eungdamrong, C. Fisher, F. Peng, L. Mahadevan, T. Mitchison and S. Kuo,  Current Biology , 13 (1-20), 1-6, 2003. [View PDF] [Download PDF]
Microtubules can bear enhanced compressive loads in living cells because of lateral reinforcements C. Brangwynne, F. Mackintosh, S. Kumar, N. Geisse, J. Talbot, L. Mahadevan, K. Parker, D. Ingber and D. Weitz,  Journal of Cell Biology  , 173, 733, 2006. [View PDF] [Download PDF]
A quantitative analysis of contractility in active cytoskeletal protein networks P. Bendix, G. Koenderink, D. Cuvelier, Z. Dogic, B. Koeleman, W. Brieher, C. Field, L. Mahadevan and D. Weitz,  Biophysical Journal,  94, 3126, 2008. [View PDF] [Download PDF]
Molecular control of macroscopic forces drives formation of the vertebrate hindgut N.L. Nerurkar, CH Lee, L. Mahadevan & C.J. Tabin, Nature 565, 2019. [DOI] [View PDF] [Download PDF]
Elastic model of a DNA loop in the lac operon,  Balaeff, A., L. Mahadevan, and K. Schulten,  Physical Review Letters , 83, 4900-03, 1999. [View PDF] [Download PDF]
Modeling DNA loops using the theory of elasticity A. Balaeff, L. Mahadevan and K. Schulten,  Physical Review E,  73, 031919, 2006. [View PDF] [Download PDF]
Multiscale methods for modeling protein-DNA complexes, Villa, E. , Balaeff, A., L. Mahadevan and K. Schulten,  SIAM Multiscale Modeling and Simulation , 2, 527-553 (2004). [View PDF] [Download PDF]
Force of an actin spring J.H. Shin, B.K. Tam, R.R. Brau, M.J. Lang, L. Mahadevan, and Paul Matsudaira,  Biophysical Journal , 92, 3729, 2007. [View PDF] [Download PDF]
Structural model for cooperative DNA binding by CAP and Lac repressor, Balaeff, A., L. Mahadevan and K. Schulten,  Structure , 12, 123-32, 2004. [DOI] [View PDF] [Download PDF]
Dynamics of chromatin decondensation reveals the structural integrity of a mechanically prestressed nucleus  A. Mazumder, T. Roopa, A. Basu, L. Mahadevan, and G. Shivashankar,  Biophysical Journal , 95, 3028, 2008. [View PDF] [Download PDF]
Elastic behavior of cross-linked and bundled actin networks,  Gardel, M., J. Shin, F. Mackintosh, L. Mahadevan, P. Matsudaira and D. Weitz,  Science,  304, 1301-5, 2004. [View PDF] [Download PDF]
Calcium regulation of an actin spring B. Tam, J. Shin, E. Pfeiffer, P. Matsudaira and L. Mahadevan,  Biophysical Journal , 97, 1125, 2009. [View PDF] [Download PDF]
Actin network growth under load O. Campàs, L. Mahadevan, and J-F. Joanny,  Biophysical Journal , 102, 1049-1058, 2012. [View PDF] [Download PDF]
Power-limited contraction dynamics of Vorticella convallaria: an ultrafast biological spring A. Upadhyaya, M. Baraban, J. Wong, P. Matsudaira, A. van Oudenaarden and L. Mahadevan,  Biophysical Journal , 94, 265, 2008. [View PDF] [Download PDF]
Scaling of F-actin rheology to probe single filament elasticity and dynamics, Gardel, M., J. Shin, F. Mackintosh, L. Mahadevan, P. Matsudaira and D. Weitz,  Physical Review Letters , 93, 188102, 2004. [View PDF] [Download PDF]
Elastic instability-mediated actuation by a supra-molecular polymer A. Levin, T. C. T. Michaels, L. Adler-Abramovich, T. O. Mason, T. Müller, B. Zhang, L. Mahadevan, E. Gazit, and T. P. J. Knowles.  Nature Physics , 12, 926-30, 2016. [View PDF] [Download PDF]
Stored elastic energy powers the 60-micron extension of the Limulus polyphemus sperm actin bundle, Shin, J., L. Mahadevan, G. Waller, K. Langsmo and P. Matsudaira,  Journal of Cell Biology , 162(7), 1183-88, 2003. [View PDF] [Download PDF]