Publications

We present a direct derivation of the typical time derivatives used in a continuum description of complex fluid flows{,} harnessing the principles of the kinematics of line elements. The evolution of the microstructural conformation tensor in a flow and the physical interpretation of different derivatives then follow naturally.

Study question:
Is there any relationship between the relative telomere length (RTL) within cumulus cells (CCs) and the outcome of assisted reproductive treatment using the corresponding oocyte?

Summary answer:
Lower RTLs in CCs were significantly associated with embryos chosen for transfer or cryopreservation. In contrast, embryos considered non-viable (discarded) tended to have higher RTLs.

During eukaryotic cell division, microtubules connect to chromosomes by attaching to the kinetochore via the NDC80 complex (NDC80c). The regulation of kinetochore microtubule (KMT) detachment is crucial for correcting mitotic errors. Here, we investigate the mechanism of KMT detachment by combining photoconversion measurements of KMT detachment rate, FLIM-FRET measurements of NCD80c/KMT binding, and mathematical modeling. Our results support a dual detachment mechanism in which KMTs detach from kinetochores when either 1) all NDC80c spontaneously unbind from the KMT or 2) following KMT catastrophe. We identify kinetochore components that selectively impact these two mechanisms and show that the affinity of NDC80c for KMTs is reduced at low-tension, non-bioriented kinetochores due to centromere-localized Aurora B phosphorylating the NDC80c, resulting in an elevated detachment rate for the associated KMTs. Taken together, this work leads to a biophysical model for the molecular basis of KMT detachments and their regulation during mitotic error correction.

Active colloidal systems with nonequilibrium self-organization constitute a long-standing, challenging area in material sciences and biology. To understand how hydrodynamic flow may be used to actively control self-assembly of Janus particles (JPs), we developed a model for the many-body hydrodynamics of amphiphilic JPs suspended in a viscous fluid with imposed far-field background flows [Fu et al., J. Fluid Mech. 941, A41 (2022)]. In this paper we alter the hydrophobic distribution on the JP-solvent interface to investigate the hydrodynamics that underlies the various morphologies and rheological properties of the JP assembly in the suspension. We find that JPs assemble into unilamellar, multilamellar, and striated structures. To introduce dynamics, we include a planar linear shear flow and a steady Taylor-Green mixing flow and measure the collective dynamics of JP particles in terms of their (a) free energy from the hydrophobic interactions between the JPs, (b) order parameter for the ordering of JPs in terms of alignment of their directors, and (c) strain parameter that captures the deformation in the assembly. We characterize the effective material properties of the JP structures and find that the unilamellar structure increases orientation order under shear flow, the multilamellar structure behaves as a shear thinning fluid, and the striated structure possesses a yield stress. These numerical results provide insights into dynamic control of nonequilibrium active biological systems with similar self-organization.

Life is a nonequilibrium phenomenon: Metabolism provides a continuous supply of energy that drives nearly all cellular processes. However, very little is known about how much energy different cellular processes use, i.e., their energetic costs. The most direct experimental measurements of these costs involve modulating the activity of cellular processes and determining the resulting changes in energetic fluxes. In this review, we present a flux balance framework to aid in the design and interpretation of such experiments and discuss the challenges associated with measuring the relevant metabolic fluxes. We then describe selected techniques that enable measurement of these fluxes. Finally, we review prior experimental and theoretical work that has employed techniques from biochemistry and nonequilibrium physics to determine the energetic costs of cellular processes.

Life in complex systems, such as cities and organisms, comes to a standstill when global coordination of mass, energy, and information flows is disrupted. Global coordination is no less important in single cells, especially in large oocytes and newly formed embryos, which commonly use fast fluid flows for dynamic reorganization of their cytoplasm. Here, we combine theory, computing, and imaging to investigate such flows in the Drosophila oocyte, where streaming has been proposed to spontaneously arise from hydrodynamic interactions among cortically anchored microtubules loaded with cargo-carrying molecular motors. We use a fast, accurate, and scalable numerical approach to investigate fluid-structure interactions of 1000s of flexible fibers and demonstrate the robust emergence and evolution of cell-spanning vortices, or twisters. Dominated by a rigid body rotation and secondary toroidal components, these flows are likely involved in rapid mixing and transport of ooplasmic components.

A major challenge in ART is to select high-quality oocytes and embryos. The metabolism of oocytes and embryos has long been linked to their viability, suggesting the potential utility of metabolic measurements to aid in selection. Here, we review recent work on noninvasive metabolic imaging of cumulus cells, oocytes, and embryos. We focus our discussion on fluorescence lifetime imaging microscopy (FLIM) of the autofluorescent coenzymes NAD(P)H and flavine adenine dinucleotide (FAD+), which play central roles in many metabolic pathways. FLIM measurements provide quantitative information on NAD(P)H and FAD+ concentrations and engagement with enzymes, leading to a robust means of characterizing the metabolic state of cells. We argue that FLIM is a promising approach to aid in oocyte and embryo selection.

Living systems are intrinsically nonequilibrium: They use metabolically derived chemical energy to power their emergent dynamics and self-organization. A crucial driver of these dynamics is the cellular cytoskeleton, a defining example of an active material where the energy injected by molecular motors cascades across length scales, allowing the material to break the constraints of thermodynamic equilibrium and display emergent nonequilibrium dynamics only possible due to the constant influx of energy. Notwithstanding recent experimental advances in the use of local probes to quantify entropy production and the breaking of detailed balance, little is known about the energetics of active materials or how energy propagates from the molecular to emergent length scales. Here, we use a recently developed picowatt calorimeter to experimentally measure the energetics of an active microtubule gel that displays emergent large-scale flows. We find that only approximately one-billionth of the system’s total energy consumption contributes to these emergent flows. We develop a chemical kinetics model that quantitatively captures how the system’s total thermal dissipation varies with ATP and microtubule concentrations but that breaks down at high motor concentration, signaling an interference between motors. Finally, we estimate how energy losses accumulate across scales. Taken together, these results highlight energetic efficiency as a key consideration for the engineering of active materials and are a powerful step toward developing a nonequilibrium thermodynamics of living systems.

Many active particles, such as swimming micro-organisms or motor proteins, do work on their environment by going though a periodic sequence of shapes. Interactions between particles can lead to synchronization of their duty cycles. Here, we study the collective dynamics of a suspension of active particles coupled through hydrodynamics. We find that at high enough density the system transitions to a state of collective motion by a mechanism that is distinct from other instabilities in active matter systems. Second, we demonstrate that the emergent nonequilibrium states feature stationary chimera patterns in which synchronized and phase-isotropic regions coexist. Third, we show that in confinement, oscillatory flows and robust unidirectional pumping states exist, and can be selected by choice of alignment boundary conditions. These results point toward a new route to collective motion and pattern formation and could guide the design of new active materials.

During cell division, the mitotic spindle forms inside cells and segregates chromosomes. The spindle's position sets the division plane, which is essential for proper growth and development. Force mechanisms regulating the position of the spindle are not yet understood. Here, we develop a coarse-grained model of spindles in cells, which accounts for microtubule dynamics, pulling forces from cortically bounded motor proteins, and fluid drag. We show that the spindle's resistance to rotation is largely driven by pulling forces from the motor proteins rather than the drag imposed by the cytoplasm. We also show that the arrangement of motor proteins affects the spindle's resistance to rotation for configurations where multiple motors stack at the same region, the spindle's resistance to rotation significantly reduces. Our findings are consistent with measurements in human tissue culture cells, where the spindle resistance to the rotation has been quantified.