Active Mechanics of the Actin Cortex

The actomyosin cortex generates contractile stresses which in turn drive mechanical deformation at the cellular and tissue scales. How does this cellular-scale deformation emerge from the protein-scale interactions between the cortex's constituents? Together with Nikta Fakhri and Sebastian Fürthauer, we're addressing this question using starfish oocytes as a model system.

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Thermodynamics of Active Materials

Active materials are driven out of equilibrium by the conversion of energy into directional motion at the scale of the system's constituents. How much energy do active materials consume, and what fraction of this energy goes into large scale motion? In collaboration with Jinhye Bae, Joost Vlassak, Dan Needleman, and Zvonimir Dogic, we are using calorimetry to directly measure heat flow in a microtubule-based active material.

J Bae*, J Zheng*, H Zhang, PJ Foster, DJ Needleman, JJ Vlassak, "A Micromachined Picocalorimeter Sensor for Liquid Samples with Application to Chemical Reactions and Biochemistry", Adv. Sci., 2021; 8; 2003415; doi:10.1002/advs.202003415                                            (* denotes co-first authors)

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Active Contraction of Microtubule Networks

We discovered that networks composed of stabilized microtubules in Xenopus oocyte extract undergo a spontaneous contraction on the millimeter length scale, due to the clustering of microtubule minus ends by the motor protein dynein. In collaboration with Michael Shelley and Sebastian Fürthauer at NYU, we developed an Active Fluid model that can quantitatively describe the contraction process.

PJ Foster, S Fürthauer, MJ Shelley, DJ Needleman, “Active contraction of microtubule networks”, eLife 2015;4:e10837; doi:10.7554/eLife.10837

PJ Foster*, W Yan*, S Fürthauer, MJ Shelley, DJ Needleman, "Connecting macroscopic dynamics with microscopic properties in active microtubule network contraction", New J. Phys. 2017; 19; 125011; doi:10.1088/1367-2630/aa9320    (* denotes co-first authors)

​PJ Foster, S Fürthauer, MJ Shelley, DJ Needleman, "From cytoskeletal assemblies to living materials", Curr. Opin. Cell Biol. 2019; 56; 109-114; doi:10.1016/j.ceb.2018.10.010

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Collective Organization of Microtubules and Motors

In vitro systems of purified microtubules and motor proteins offer a greater degree of biochemical control compared with living systems. Can bulk microtubule network contractions be recapitulated with purified motors? In collaboration with Richard McKenney at UC Davis and Claire Walczak at IU we studied the collective behaviors of microtubules and motors proteins.

S Fürthauer, B Lemma, PJ Foster, SC Ems-McClung, CH Yu, CE Walczak, Z Dogic, DJ Needleman, MJ Shelley, "Self-straining of actively crosslinked microtubule networks", Nat. Phys. 2019; 15; 1295-1300; doi:10.1038/s41567-019-0642-1

​R Tan, PJ Foster, DJ Needleman, RJ McKenney, "Cooperative Accumulation of Dynein-Dynactin at Microtubule Minus-Ends Drives Microtubule Network Reorganization", Dev. Cell 2018; 44(2); 233-247; doi:10.1016/j.devcel.2017.12.023 ​

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Bayesian Analysis of FLIM Data

Fluorescence Lifetime Imaging Microscopy (FLIM) is a spectroscopic method where changes in the lifetime of a fluorophore are used to infer changes in the fluorophore's local environment. How can one cope with noisy FLIM data? One approach is to use Bayesian inference to combine measured data with knowledge about the system. I helped to develop and test a FLIM analysis technique based on Bayesian statistics, which can be used to accurately infer fluorescence decay parameters in noisy regimes. This approach was then used to develop a technique to measure polymer assembly in cells and cell extracts.

​B Kaye*, PJ Foster*, TY Yoo*, DJ Needleman, "Developing and Testing a Bayesian Analysis of Fluorescence Lifetime Measurements",PLoS ONE 2017;12(1);e0169337;
​doi:10.1371/journal.pone.0169337      (* denotes co-first authors)

B Kaye, TY Yoo, PJ Foster, CH Yu, DJ Needleman, "Bridging length scales to measure polymer assembly", Mol. Biol. Cell 2017; 28(10); 1379-1388; doi:10.1091/mbc.E16-05-0344

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Spindle Dynamics and Organization

Spindles are biochemically complex environments where many different kinds of proteins and complexes act in concert to organize dynamic microtubules. What framework can be used to understand the collective effects of these biochemical interactions and to understand effects on the spindle-scale in terms of the interactions between individual components?

B Kaye, O Steihl, PJ Foster, MJ Shelley, DJ Needleman, S Fürthauer, "Measuring and modeling polymer gradients argues that spindle microtubules regulate their own nucleation", New J. Phys. 2018; 20; 055012; doi:10.1088/1367-2630/aac2a5

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Lipopolysaccharide Transport

In gram-negative bacteria, the outer leaflet of the outer membrane is largely composed of the large glycolipid lipopolysaccharide (LPS). How is LPS transported from its site of synthesis in the cytoplasm through the inner membrane, the periplasm, and the inner leaflet of the outer membrane to arrive at the outer leaflet? In collaboration with Dan Kahne at Harvard, we’re working to study this problem using biochemical, spectroscopic, and microscopy methods.

 DJ Sherman*, R Xie*, RJ Taylor*, AH George*, S Okuda*, PJ Foster*, DJ Needleman, D Kahne, "Lipopolysaccharide is transported to the cell surface by a membrane-to-membrane protein bridge", Science, 2018; 359(6377); 798-801; doi:10.1126/science.aar1886
                                                                                                                                ​(* denotes co-first authors)