Mechanotransduction of mitochondrial AMPK and its distinct role in flow-induced breast cancer cell migration

The biophysical microenvironment of the tumor site has significant impact on breast cancer progression and metastasis. The importance of altered mechanotransduction in cancerous tissue has been documented, yet its role in the regulation of cellular metabolism and the potential link between cellular energy and cell migration remain poorly understood. In this study, we investigated the role of mechanotransduction in AMP-activated protein kinase (AMPK) activation in breast cancer cells in response to interstitial fluid flow (IFF). Additionally, we explored the involvement of AMPK in breast cancer cell migration. IFF was applied to the 3D cell-matrix construct. The subcellular signaling activity of Src, FAK, and AMPK was visualized in real-time using fluorescent resonance energy transfer (FRET). We observed that breast cancer cells (MDA-MB-231) are more sensitive to IFF than normal epithelial cells (MCF-10A). AMPK was activated at the mitochondria of MDA-MB-231 cells by IFF, but not in other subcellular compartments (i.e., cytosol, plasma membrane, and nucleus). The inhibition of FAK or Src abolished flow-induced AMPK activation in the mitochondria of MDA-MB-231 cells. We also observed that global AMPK activation reduced MDA-MB-231 cell migration. Interestingly, specific AMPK inhibition in the mitochondria reduced cell migration and blocked flow-induced cell migration. Our results suggest the linkage of FAK/Src and mitochondria-specific AMPK in mechanotransduction and the differential role of AMPK in breast cancer cell migration depending on its subcellular compartment-specific activation

Identification of candidate genes involved in wax deposition in Poa pratensis by RNA-seq

A, Randomness test of cDNA fragments; B, Sequencing saturation analysis. T1 and T2 represent NEZm; T3 and T4 represent EBZ. (PDF 290 kb

RISE-Based Integrated Motion Control of Autonomous Ground Vehicles With Asymptotic Prescribed Performance

This article investigates the integrated lane-keeping and roll control for autonomous ground vehicles (AGVs) considering the transient performance and system disturbances. The robust integral of the sign of error (RISE) control strategy is proposed to achieve the lane-keeping control purpose with rollover prevention, by guaranteeing the asymptotic stability of the closed-loop system, attenuating systematic disturbances, and maintaining the controlled states within the prescribed performance boundaries. Three contributions have been made in this article: 1) a new prescribed performance function (PPF) that does not require accurate initial errors is proposed to guarantee the tracking errors restricted within the predefined asymptotic boundaries; 2) a modified neural network (NN) estimator which requires fewer adaptively updated parameters is proposed to approximate the unknown vertical dynamics; and 3) the improved RISE control based on PPF is proposed to achieve the integrated control objective, which analytically guarantees both the controller continuity and closed-loop system asymptotic stability by integrating the signum error function. The overall system stability is proved with the Lyapunov function. The controller effectiveness and robustness are finally verified by comparative simulations using two representative driving maneuvers, based on the high-fidelity CarSim-Simulink simulation