More Like this

1. Size of the protein-protein energy funnel in crowded environment

   https://doi.org/10.3389/fmolb.2022.1031225  

   Jenkins, Nathan W.; Kundrotas, Petras J.; Vakser, Ilya A. (November 2022, Frontiers in Molecular Biosciences)

   Association of proteins to a significant extent is determined by their geometric complementarity. Large-scale recognition factors, which directly relate to the funnel-like intermolecular energy landscape, provide important insights into the basic rules of protein recognition. Previously, we showed that simple energy functions and coarse-grained models reveal major characteristics of the energy landscape. As new computational approaches increasingly address structural modeling of a whole cell at the molecular level, it becomes important to account for the crowded environment inside the cell. The crowded environment drastically changes protein recognition properties, and thus significantly alters the underlying energy landscape. In this study, we addressed the effect of crowding on the protein binding funnel, focusing on the size of the funnel. As crowders occupy the funnel volume, they make it less accessible to the ligands. Thus, the funnel size, which can be defined by ligand occupancy, is generally reduced with the increase of the crowders concentration. This study quantifies this reduction for different concentration of crowders and correlates this dependence with the structural details of the interacting proteins. The results provide a better understanding of the rules of protein association in the crowded environment. 

   more » « less
2. Accretion Funnel Reconfiguration during an Outburst in a Young Stellar Object: EX Lupi

   https://doi.org/10.3847/1538-4357/ad4099  

   Singh, Koshvendra; Ninan, Joe_P; Romanova, Marina_M; Buckley, David_A_H; Ojha, Devendra_K; Ghosh, Arpan; Monson, Andrew; Schramm, Malte; Sharma, Saurabh; Reichart, Daniel_E; et al (June 2024, The Astrophysical Journal)

   Abstract EX Lupi, a low-mass young stellar object, went into an accretion-driven outburst in 2022 March. The outburst caused a sudden phase change of ∼112° ± 5° in periodically oscillating multiband lightcurves. Our high-resolution spectra obtained with the High Resolution Spectrograph (HRS) on board the Southern African Large Telescope also revealed a consistent phase change in the periodically varying radial velocities (RVs), along with an increase in the RV amplitude of various emission lines. The phase change and increase in RV amplitude morphologically translates to a change in the azimuthal and latitudinal location of the accretion hotspot over the stellar surface, which indicates a reconfiguration of the accretion funnel geometry. Our three-dimensional magnetohydrodynamic simulations reproduce the phase change for EX Lupi. To explain the observations, we explored the possibility of forward shifting of the dipolar accretion funnel as well as the possibility of the emergence of a new accretion funnel. During the outburst, we also found evidence of the hotspot’s morphology extending azimuthally asymmetrically with a leading hot edge and cold tail along the stellar rotation. Further, our high-cadence photometry showed that the accretion flow has clumps. We also detected possible clumpy accretion events in the HRS spectra that showed episodically highly blueshifted wings in the CaiiIR triplet and Balmer H lines. 

   more » « less
3. Physics-guided hierarchical Neural Networks for Maxwell’s equations in metamaterials

   https://doi.org/10.1364/CLEO_FS.2024.FW4Q.2  

   Lynch, Sean; LaMountain, Jacob; Fan, Bo; Bu, Jie; Raju, Amogh; Wasserman, Daniel; Karpatne, Anuj; Podolskiy, Viktor (January 2024, Optica Publishing Group)

   We develop a hierarchical approach to building a Physics-guided neural network (PGNN) for scalable solutions of Maxwell equations with high spatial resolution and illustrate the developed formalism on a metamaterial photonic funnel example. 

   more » « less
4. One size does not fit all: diversity of length–force properties of obliquely striated muscles

   https://doi.org/10.1242/jeb.244949  

   Thompson, Joseph T.; Taylor-Burt, Kari R.; Kier, William M. (April 2023, Journal of Experimental Biology)

   ABSTRACT Obliquely striated muscles occur in 17+ phyla, likely evolving repeatedly, yet the implications of oblique striation for muscle function are unknown. Contrary to the belief that oblique striation allows high force output over extraordinary length ranges (i.e. superelongation), recent work suggests diversity in operating length ranges and length–force relationships. We hypothesize oblique striation evolved to increase length–force relationship flexibility. We predict that superelongation is not a general characteristic of obliquely striated muscles and instead that length–force relationships vary with operating length range. To test these predictions, we measured length–force relationships of five obliquely striated muscles from inshore longfin squid, Doryteuthis pealeii: tentacle, funnel retractor and head retractor longitudinal fibers, and arm and fin transverse fibers. Consistent with superelongation, the tentacle length–force relationship had a long descending limb, whereas all others exhibited limited descending limbs. The ascending limb at 0.6P0 was significantly broader (P<0.001) for the tentacle length–force relationship (0.43±0.04L0; where L0 is the preparation length that produced peak isometric stress, P0) than for the arm (0.29±0.03L0), head retractor (0.24±0.06L0), fin (0.20±0.04L0) and funnel retractor (0.27±0.03L0). The fin's narrow ascending limb differed significantly from those of the arm (P=0.004) and funnel retractor (P=0.012). We further characterized the tentacle preparation's maximum isometric stress (315±78 kPa), maximum unloaded shortening velocity (2.97±0.55L0 s−1) and ultrastructural traits (compared with the arm), which may explain its broader length–force relationship. Comparison of obliquely striated muscles across taxa revealed length–force relationship diversity, with only two species exhibiting superelongation. 

   more » « less
5. Toward Automated Additive Manufacturing of Living Bio-Tubes Using Ring-Shaped Building Units

   https://doi.org/10.1177/2472630320920896  

   Manning, Kali L.; Feder, Jacob; Kanellias, Marianne; Murphy, John; Morgan, Jeffrey R. (March 2020, SLAS TECHNOLOGY: Translating Life Sciences Innovation)

   Tissue engineering has been largely confined to academic research institutions with limited success in commercial settings. To help address this issue, more work is needed to develop new automated manufacturing processes for tissue-related technologies. In this article, we describe the automation of the funnel-guide, an additive manufacturing method that uses living tissue rings as building units to form bio-tubes. We developed a method based on 96-well plates and a modified off-the-shelf liquid-handling robot to retrieve, perform real-time quality control, and transfer tissue rings to the funnel-guide. Cells seeded into 96-well plates containing specially designed agarose micromolds self-assembled and formed ring-shaped microtissues that could be retrieved using a liquid-handling robot. We characterized the effects of time, cell type, and mold geometry on the morphology of the ring-shaped microtissues to inform optimal use of the building parts. We programmed and modified an off-the-shelf liquid-handling robot to retrieve ring-shaped microtissues from the 96-well plates, and we fabricated a custom illuminated pipette to visualize each ring-shaped microtissue prior to deposit in the funnel guide. Imaging at the liquid-air interface presented challenges that were overcome by controlling lighting conditions and liquid curvature. Based on these images, we incorporated into our workflow a real-time quality control step based on visual inspection and morphological criteria to assess each ring prior to use. We used this system to fabricate bio-tubes of endothelial cells with luminal alignment. 

   more » « less