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The extracellular matrix (ECM) regulates carcinogenesis by interacting with cancer cells via cell surface receptors. Discoidin Domain Receptor 2 (DDR2) is a collagen‐activated receptor implicated in cell survival, growth, and differentiation. Dysregulated DDR2 expression has been identified in various cancer types, making it as a promising therapeutic target. Additionally, cancer cells exhibit mechanosensing abilities, detecting changes in ECM stiffness, which is particularly important for carcinogenesis given the observed ECM stiffening in numerous cancer types. Despite these, whether collagen‐activated DDR2 signaling and ECM stiffness‐induced mechanosensing exert similar effects on cancer cell behavior and whether they operate through analogous mechanisms remain elusive. To address these questions, we performed bulk RNA sequencing (RNA‐seq) on human SH‐SY5Y neuroblastoma cells cultured on collagen‐coated substrates. Our results show that DDR2 downregulation induces significant changes in the cell transcriptome, with changes in expression of 15% of the genome, specifically affecting the genes associated with cell division and differentiation. We validated the RNA‐seq results by showing that DDR2 knockdown redirects the cell fate from proliferation to senescence. Like DDR2 knockdown, increasing substrate stiffness diminishes cell proliferation. Surprisingly, RNA‐seq indicates that substrate stiffness has no detectable effect on the transcriptome. Furthermore, DDR2 knockdown influences cellular responses to substrate stiffness changes, highlighting a crosstalk between these two ECM‐induced signaling pathways. Based on our results, we propose that the ECM could activate DDR2 signaling and mechanosensing in cancer cells to orchestrate their cell fate through distinct mechanisms, with or without involving gene expression, thus providing novel mechanistic insights into cancer progression. 

Abstract The need for operational models describing the friction factorfin streams remains undisputed given its utility across a plethora of hydrological and hydraulic applications concerned with shallow inertial flows. For small-scale roughness elements uniformly covering the wetted parameter of a wide channel, the Darcy-Weisbachf = 8(u_*/U_b)²is widely used at very high Reynolds numbers, whereu_*is friction velocity related to the surface kinematic stress,U_b = Q/Ais bulk velocity,Qis flow rate, andAis cross-sectional area orthogonal to the flow direction. In natural streams, the presence of vegetation introduces additional complications to quantifyingf, the subject of the present work. Turbulent flow through vegetation are characterized by a number of coherent vortical structures: (i) von Karman vortex streets in the lower layers of vegetated canopies, (ii) Kelvin-Helmholtz as well as attached eddies near the vegetation top, and (iii) attached eddies well above the vegetated layer. These vortical structures govern the canonical mixing lengths for momentum transfer and their influence onfis to be derived. The main novelty is that the friction factor of vegetated flow can be expressed asf_v = 4C_d(U_v/U_b)²whereU_vis the spatially averaged velocity within the canopy volume, andC_dis a local drag coefficient per unit frontal area derived to include the aforemontioned layer-wise effects of vortical structures within and above the canopy along with key vegetation properties. The proposed expression is compared with a number of empirical relations derived for vegetation under emergent and submerged conditions as well as numerous data sets covering a wide range of canopy morphology, densities, and rigidity. It is envisaged that the proposed formulation be imminently employed in eco-hydraulics where the interaction between flow and vegetation is being sought. 

Quantification of roughness effects on free surface flows is unquestionably necessary when describing water and material transport within ecosystems. The conventional hydrodynamic resistance formula empirically shows that the Darcy–Weisbach friction factor f~(r/hw)1/3 describes the energy loss of flowing water caused by small-scale roughness elements characterized by size r (<