Browsing by Author "Li, Wen"

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    Perlecan-Containing Pericellular Matrix Regulates Solute Transport and Mechanosensing Within the Osteocyte Lacunar-Canalicular System
    (Wiley, 2014) Wang, Bin; Lai, Xiaohan; Price, Christopher; Thompson, William R.; Li, Wen; Quabili, Tonima R.; Tseng, Wei-Ju; Liu, Xiaowei Sherry; Zhang, Hong-Yi; Pan, Jun; Kirn-Safran, Catherine B.; Farach-Carson, Mary C.; Wang, Liyun
    The pericellular matrix (PCM), a thin coating surrounding nearly all mammalian cells, plays a critical role in many cell-surface phenomena. In osteocytes, the PCM is believed to control both “outside-in” (mechanosensing) and “inside-out” (signaling molecule transport) processes. However, the osteocytic PCM is challenging to study in situ because it is thin (∼100 nm) and enclosed in mineralized matrix. To this end, we recently developed a novel tracer velocimetry approach that combined fluorescence recovery after photobleaching (FRAP) imaging with hydrodynamic modeling to quantify the osteocytic PCM in young murine bone. In this study, we applied the technique to older mice expressing or deficient for perlecan/HSPG2, a large heparan-sulfate proteoglycan normally secreted in osteocytic PCM. The objectives were (1) to characterize transport within an altered PCM; (2) to test the sensitivity of our approach in detecting the PCM alterations; and (3) to dissect the roles of the PCM in osteocyte mechanosensing. We found that: (1) solute transport increases in the perlecan-deficient (hypomorphic [Hypo]) mice compared with control mice; (2) PCM fiber density decreases with aging and perlecan deficiency; (3) osteocytes in the Hypo bones are predicted to experience higher shear stress (+34%), but decreased fluid drag force (−35%) under 3-N peak tibial loading; and (4) when subjected to tibial loading in a preliminary in vivo experiment, the Hypo mice did not respond to the anabolic stimuli as the CTL mice did. These findings support the hypothesis that the PCM fibers act as osteocyte's sensing antennae, regulating load-induced cellular stimulations and thus bone's sensitivity and in vivo bone adaptation. If this hypothesis is further confirmed, osteocytic PCM could be new targets to develop osteoporosis treatments by modulating bone's intrinsic sensitivity to mechanical loading and be used to design patient-specific exercise regimens to promote bone formation.
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    Simulation of radiation belt wave-particle interactions in an MHD-particle framework
    (Frontiers Media S.A., 2023) Chan, Anthony A.; Elkington, Scot R.; Longley, William J.; Aldhurais, Suhail A.; Alam, Shah S.; Albert, Jay M.; Jaynes, Allison N.; Malaspina, David M.; Ma, Qianli; Li, Wen
    In this paper we describe K2, a comprehensive simulation model of Earth’s radiation belts that includes a wide range of relevant physical processes. Global MHD simulations are combined with guiding-center test-particle methods to model interactions with ultra low-frequency (ULF) waves, substorm injections, convective transport, drift-shell splitting, drift-orbit bifurcations, and magnetopause shadowing, all in self-consistent MHD fields. Simulation of local acceleration and pitch-angle scattering due to cyclotron-scale interactions is incorporated by including stochastic differential equation (SDE) methods in the MHD-particle framework. The SDEs are driven by event-specific bounce-averaged energy and pitch-angle diffusion coefficients. We present simulations of electron phase-space densities during a simplified particle acceleration event based on the 17 March 2013 event observed by the Van Allen Probes, with a focus on demonstrating the capabilities of the K2 model. The relative wave-particle effects of global scale ULF waves and very-low frequency (VLF) whistler-mode chorus waves are compared, and we show that the primary acceleration appears to be from the latter. We also show that the enhancement with both ULF and VLF processes included exceeds that of VLF waves alone, indicating a synergistic combination of energization and transport processes may be important.