Publications:
2024 - Incorporating the diffusivity gradient term in Brownian dynamics simulations of diffusion
Rikki M. Garner*, Arthur T. Molines*, Julie A. Theriot, Fred Chang.
Biophysical Journal, DOI: 10.1016/j.bpj.2024.07.032
https://www.cell.com/biophysj/fulltext/S0006-3495(24)00491-0
In this paper, we addressed concerns raised by Dr. Skora (link) about the absence of the diffusivity gradient in the model we had published earlier in Garner, Molines et al., 2023 (link). Without this diffusivity gradient term, particles are predicted to tend to accumulate in regions with low diffusivity (i.e., high viscosity), which may lead to underestimation of the mean and overestimation of the variance in the particle diffusivity distributions in the model. In this work, we demonstrated that the introduction of the viscosity gradient has a negligible effect on our original observation and does not change the conclusion regarding the high amount of heterogeneity in cytoplasmic viscosity.
2024 - Microtubule dynamic instability is sensitive to specific biological viscogens in vitro
Arthur T. Molines*, Claire H. Edrington*, Sofía Cruz Tetlalmatzi, Fred Chang, Gary J. Brouhard
*Equal co-first authors with swappable positions.
bioRXiv, DOI: https://doi.org/10.1101/2024.05.27.596091
https://www.biorxiv.org/content/10.1101/2024.05.27.596091v1
This paper is a collaboration between the Chang's lab at UCSF) and the Brouhard’s lab at McGill. This work is a follow up of our work on the effect of viscosity on microtubule dynamics in vivo (Molines et al., 2022, Dev. Cell) and a continuation of the work from Gary Brouhard’s lab on viscosity and crowding effect in vitro (Wieczoreck et al., 2013, Cell. and Mol. Bioeng.). We used in vitro reconstitution of microtubule dynamics to study the effect of different viscogens on microtubule dynamics. We used three biologically relevant viscogens; glycerol, trehalose and BSA (bovine serum albumin) and compared how they affect microtubule dynamic instability.
2022 - A unified model for the dynamics of ATP-independent ultrafast contraction
Carlos Floyd, Arthur T. Molines, Xiangting Lei, Jerry E. Honts, Fred Chang, Mary Williard Elting, Suriyanarayanan Vaikuntanathan, Aaron R. Dinner, and M. Saad Bhamla
PNAS, DOI: https://doi.org/10.1073/pnas.2217737120
https://www.pnas.org/doi/10.1073/pnas.2217737120
This paper is the result of a collaboration between multiple labs. Our main goal was to obtain a computational model of the ultrafast contraction happening in some unicellular ciliates. This contraction is ATP-independent and powered by the myonemes fibers that run along the length of the cell. The contraction is induced by an increase in intracellular calcium that forms a wave that travels from one end the cell to the other. We used high-speed imaging to image the contractions events and compare them to the model predictions. Our minimal mathematical model can reproduce the experimental results and reveals a set of three dynamic regimes, which are differentiated by the rate of chemical driving and the importance of inertia
2023 - Vast heterogeneity in cytoplasmic diffusion rates revealed by nanorheology and Doppelgänger simulations
Arthur T. Molines*, Rikki M. Garner*, Julie A. Theriot, Fred Chang.
*Equal co-first authors with swappable positions.
Biophysical Journal, DOI: https://doi.org/10.1101/2022.05.11.491518
https://www.cell.com/biophysj/fulltext/S0006-3495(23)00089-9
This paper is a collaboration between me in Fred Chang's lab (UCSF) and Rikki Garner in Julie Theriot's lab (UW). The collaboration started in Woods Hole during my participation in the PBOC course where Rikki and Julie were TAing. We used particle tracking on the GEMs nanoparticles to study the cytoplasm properties in fission yeast. We found that GEMs diffusion is extremely variable inside cells and also between cells. Using stochastic simulations to recapitulate the experimental data, we discovered that the cytoplasm is a heterogenous environment where viscosity varies.
2022 - Physical properties of the cytoplasm modulate the rates of microtubule growth and shrinkage.
Arthur T. Molines, Joël Lemière, Claire H. Edrington, Chieh-Ting Hsu, Ida Emilie Steinmark, Klaus Suhling,
Gohta Goshima, Liam J. Holt, Gary Brouhard, Fred Chang.
Developmental Cell.
https://doi.org/10.1016/j.devcel.2022.02.001
This paper results from my main postdoctoral project in Fred Chang's lab (UCSF). We discovered that microtubule dynamics is sensitive to the viscosity of the environment; higher viscosity leading to slower dynamic. We realized that we could change cytoplasm concentration acutely using osmotic shocks and that these changes influence microtubule dynamics. We found that the main parameter changed by osmotic shocks was cytoplasm viscosity. We confirm in vitro that varying viscosity could recapitulate the effects we observed on microtubules in cells. We also demonstrate that this phenomenon is general, as we could induce similar effects in plant and mammalian cells.
2020 - Plant and mouse EB1 proteins have opposite intrinsic properties on the dynamic instability of microtubules.
Arthur T. Molines, Virginie Stoppin-Mellet, Isabelle Arnal, Frédéric M Coquelle
BMC Research Note,
https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-020-05139-6
This paper results from a collaboration between my Ph.D. supervisor Dr. Frédéric Coquelle, and Isabelle Arnal's lab at the GIN. We expressed the EB1 protein from Arabidopsis thaliana in E.coli and then purified it. We then used in vitro reconstitution assays to compare its effect on microtubule dynamics to the mammalian EB1 protein. We discovered that the plant EB1 had opposite effects on microtubules and acts more as a stabilizer.
2018 - EB1 contributes to microtubule bundling and organization, along with root growth, in Arabidopsis thaliana.
Arthur T. Molines, Jessica Marion, Salem Chabout, Laetitia Besse, Jim P. Dompierre,
Grégory Mouille, Frédéric M. Coquelle.
Biology Open 2018 7: bio030510 DOI: 10.1242/bio.030510
This paper is the main result of my Ph.D. work with Dr. Frédéric Coquelle at Saclay University. The protein EB1 is a well-known regulator of microtubule dynamics in yeast, fly, and mammals. We studied the roles of its ortholog in Arabidopsis thaliana on microtubule dynamics and organization. We discovered that EB1 has little effect on microtubule dynamics in Arabidopsis but contributes to the organization of the microtubule network. In absence of EB1, the microtubule network is disorganized and has fewer microtubules per bundle. The mutant plants in which EB1 is knocked-out have macroscopic effects that could result from the sub-cellular phenotypes we observed.
2016 - Cortical Microtubules Network Organization in Arabidopsis thaliana: Contribution of EB1 and MAP65-1 proteins.Arthur Molines. Thesis manuscript. Paris-Saclay University, 2016. French. <NNT : 2016SACLS421>. <tel-01446716>HAL Id : tel-01446716, version 1. https://tel.archives-ouvertes.fr/tel-01446716
This is my Ph.D. dissertation. It is the culmination of my years of research and training under the supervision of Dr. Frédéric Coquelle.