Physics of Cellular Systems

   Published Research


Endoplasmic reticulum network


Search times on mitochondrial networks

Diffusion in intracellular compartments
Cellular organelles provide confined microenvironments, including the tubular networks of the endoplasmic reticulum and mitochondria. The size and topology of these organelles control search timescales and chemical kinetics. This work emphasizes the ability of physical size and shape to regulate biological activity.

Related publications:

Impact of global structure on diffusive exploration of organelle networks. A. I. Brown, L. M. Westrate, and E. F. Koslover. Sci. Rep. 10: 4984 (2020) [PDF | Journal]

Mitochondrial Fission and fusion dynamics generate efficient, robust, and evenly distributed network topologies in budding yeast cells. M. P. Viana, A. I. Brown, I. A. Mueller, C. Goul, E. F. Koslover, and S. M. Rafelski. Cell Syst. 10: 287-297 (2020) [Journal]

Getting around the cell: physical transport in the intracellular world. S. S. Mogre, A. I. Brown, and E. F. Koslover. Phys. Biol. In press [Journal]

Single file diffusion into a semi-infinite tube. S. G. Farrell, A. I. Brown, and A. D. Rutenberg. Phys. Biol., 12: 064001 (2015) [PDF | Journal]


Nucleosome organization


DNA-protein interaction energy

Energy barriers in cell biology
DNA transcription involves a 'polymerase' machine that walks along DNA copying the letters into RNA. DNA in the nucleus is organized into structures that present an energy barrier to transcription by the polymerase. By combining sophisticated experiments with computational modeling, this energy barrier can be probed and related to gene expression phenomena.

Related publications:

High-resolution and high-accuracy topographic and transcriptional maps of the nucleosome barrier. Z. Chen, R. Gabizon, A. I. Brown, A. Lee, A. Song, C. Diaz Celis, E. F. Koslover, T. Yao, and C. Bustamante. eLife, 8: 48281 (2019) [PDF | Journal]


Discrete state kinetic model of a molecular machine


ATP synthase

Molecular machine energy use
Molecular machines are effectively governed by a different set of physical rules than the much larger machines that are part of everyday life. Molecular machine operation is fundamentally nonequilibrium, and the necessary free energy expenditure can be adjusted to enhance reliable directed behavior, increase speed, and improve performance overall. This research points towards design principles that can be selected by both biological evolution and human engineers.

Related publications:

Theory of nonequilibrium free energy transduction by molecular machines. A. I. Brown and D. A. Sivak. Chem. Rev. 120: 434-459 (2020) [PDF | Journal]

Breaking time-reversal symmetry for ratchet models of molecular machines. A. Zarrin, D. A. Sivak, A. I. Brown. Phys. Rev. E, 99: 062127 (2019) [PDF | Journal]

Pulling cargo increases the precision of molecular motor progress. A. I. Brown and D. A. Sivak. Europhys. Lett., 126: 40004 (2019) [PDF | Journal]

Allocating and splitting free energy to maximize molecular machine flux. A. I. Brown and D. A. Sivak. J. Phys. Chem. B, 122: 1387-1393 (2018) [PDF | Journal]

Allocating dissipation across a molecular machine cycle to maximize flux. A. I. Brown and D. A. Sivak. Proc. Natl. Acad. Sci. USA, 114: 11057-11062 (2017) [PDF | Journal]

Toward the design principles of molecular machines. A. I. Brown and D. A. Sivak. Physics in Canada, 73: 61-66 (2017) [PDF | Journal]

Effective dissipation: breaking time-reversal symmetry in driven microscopic energy transmission. A. I. Brown and D. A. Sivak. Phys. Rev. E, 94: 032137 (2016) [PDF | Journal]


Protein cluster nucleation and evaporation


Modeling cluster growth on organelles

Protein accumulation and intracellular signaling dynamics
Cellular processes are carried through, regulated, and signaled by the accumulation of proteins on specific substrates, often forming phase-separated microdomains. Physical characteristics such as substrate size influence the diffusive search by proteins for and competition between their targets. This work highlights the physical aspects of self-organization in cell biology.

Related publications:

A model of autophagy size selectivity by receptor clustering on peroxisomes. A. I. Brown and A. D. Rutenberg. Front. Phys., 5: 14 (2017) [PDF | Journal]

Cluster coarsening on drops exhibits strong and sudden size-selectivity. A. I. Brown and A. D. Rutenberg. Soft Matter, 11: 3786-3793 (2015) [PDF | Journal]

PEX5 and ubiquitin dynamics on mammalian peroxisome membranes. A. I. Brown, P. K. Kim, and A. D. Rutenberg. PLoS Comput. Biol., 10: e1003426 (2014) [PDF | Journal]


Energy minima defining collagen fibril radii


Material diffuses to growing fibrils in collagen bundle

Collagen filament mechanics and growth
The protein collagen is an essential structural component in our bodies, organized into bundles of fibrils. Each fibril is a tube containing many collagen molecules, which can be modeled with both phase separation and liquid crystal theories. The size and growth of the collagen fibrils are subject to corresponding physical constraints.

Related publications:

Uniform spatial distribution of collagen fibril radii within tendon implies local activation of pC-collagen at individual fibrils. L. Kreplak, A. I. Brown, and A. D. Rutenberg. Phys. Biol., 13: 046008 (2016) [PDF | Journal]

An equilibrium double-twist model for the radial structure of collagen fibrils. A. I. Brown, L. Kreplak, and A. D. Rutenberg. Soft Matter, 11: 8500-8511 (2014) [PDF | Journal]


Regularly spaced heterocysts


Heterocyst spacing scaling collapse

Differentiation patterns in bacterial filaments
Heterocyst cells, which form a regularly-spaced pattern in cyanobacteria, are specialized to extract metabolically-accessible nitrogen from the atmosphere, essential to all life. Heterocyst differentiation is a model system for understanding biological pattern formation, limited to two cell types and one dimension. The generation and maintenance of the heterocyst differentiation pattern is controlled by the interplay of diffusion, growth, nutrient deficiency, and gene expression.

Related publications:

A storage-based model of heterocyst commitment and patterning in cyanobacteria. A. I. Brown and A. D. Rutenberg. Phys. Biol., 11: 016001 (2014) [PDF | Journal]

Heterocyst placement strategies to maximize the growth of cyanobacterial filaments. A. I. Brown and A. D. Rutenberg. Phys. Biol., 9: 046002 (2012) [PDF | Journal]

Reconciling cyanobacterial fixed-nitrogen distribution and transport experiments with quantitative modelling. A. I. Brown and A. D. Rutenberg. Phys. Biol., 9: 016007 (2012) [PDF | Journal]


Tat export complex dynamics


Export complex size distribution

Protein quality control
Cellular systems must discard incorrect or defective substrates to maintain their regular operation. The Tat export system exemplifies this behaviour, growing to accommodate various substrate sizes, while unbinding those that are not exportable. This work highlights one of the many quality control strategies cells use to perform in the face of an internal zoo of functional and dysfunctional macromolecules.

Related publications:

Design principles for the glycoprotein quality control pathway. A. I. Brown and E. F. Koslover. PLOS Comput. Biol., 17: e1008654 (2021) [Journal]

Protein translocation without specific quality control in a computational model of the Tat system. C. R. Nayak, A. I. Brown, and A. D. Rutenberg. Phys. Biol., 11: 056005 (2014) [PDF | Journal]