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Biomechanical effects of environmental and engineered particles on human airway smooth muscle cells

BERNTSEN, P.; PARK, C. Y.; ROTHEN-RUTISHAUSER, B.; TSUDA, A.; SAGER, T. M.; MOLINA, R. M.; DONAGHEY, T. C.; Alencar, Adriano Mesquita; KASAHARA, D. I.; ERICSSON, T.; MILLET, E. J.; SWENSON, J.; TSCHUMPERLIN, D. J.; BUTLER, J. P.; BRAIN, J. D.; FREDBERG, J
Fonte: ROYAL SOC Publicador: ROYAL SOC
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
45.82%
The past decade has seen significant increases in combustion-generated ambient particles, which contain a nanosized fraction (less than 100 nm), and even greater increases have occurred in engineered nanoparticles (NPs) propelled by the booming nanotechnology industry. Although inhalation of these particulates has become a public health concern, human health effects and mechanisms of action for NPs are not well understood. Focusing on the human airway smooth muscle cell, here we show that the cellular mechanical function is altered by particulate exposure in a manner that is dependent upon particle material, size and dose. We used Alamar Blue assay to measure cell viability and optical magnetic twisting cytometry to measure cell stiffness and agonist-induced contractility. The eight particle species fell into four categories, based on their respective effect on cell viability and on mechanical function. Cell viability was impaired and cell contractility was decreased by (i) zinc oxide (40-100 nm and less than 44 mu m) and copper(II) oxide (less than 50 nm); cell contractility was decreased by (ii) fluorescent polystyrene spheres (40 nm), increased by (iii) welding fumes and unchanged by (iv) diesel exhaust particles, titanium dioxide (25 nm) and copper(II) oxide (less than 5 mu m)...

Micropatterning of Single Endothelial Cell Shape Reveals a Tight Coupling between Nuclear Volume in G1 and Proliferation

Roca-Cusachs, Pere; Alcaraz, Jordi; Sunyer, Raimon; Samitier, Josep; Farré, Ramon; Navajas, Daniel
Fonte: The Biophysical Society Publicador: The Biophysical Society
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
45.82%
Shape-dependent local differentials in cell proliferation are considered to be a major driving mechanism of structuring processes in vivo, such as embryogenesis, wound healing, and angiogenesis. However, the specific biophysical signaling by which changes in cell shape contribute to cell cycle regulation remains poorly understood. Here, we describe our study of the roles of nuclear volume and cytoskeletal mechanics in mediating shape control of proliferation in single endothelial cells. Micropatterned adhesive islands were used to independently control cell spreading and elongation. We show that, irrespective of elongation, nuclear volume and apparent chromatin decondensation of cells in G1 systematically increased with cell spreading and highly correlated with DNA synthesis (percent of cells in the S phase). In contrast, cell elongation dramatically affected the organization of the actin cytoskeleton, markedly reduced both cytoskeletal stiffness (measured dorsally with atomic force microscopy) and contractility (measured ventrally with traction microscopy), and increased mechanical anisotropy, without affecting either DNA synthesis or nuclear volume. Our results reveal that the nuclear volume in G1 is predictive of the proliferative status of single endothelial cells within a population...

Cell tracing dyes significantly change single cell mechanics

Lulevich, Valentin; Shih, Yi-Ping; Lo, Su Hao; Liu, Gang-yu
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 07/05/2009 EN
Relevância na Pesquisa
45.93%
Cell tracing dyes are very frequently utilized in cellular biology research because they provide highly sensitive fluorescent tags that do not compromise cellular functions such as growth and proliferation. In many investigations concerning cellular adhesion and mechanics, fluorescent dyes have been employed with the assumption of little impact on the results. Using the single-cell compression technique developed by our team, the single-cell mechanics of MDA-MB-468 and MLC-SV40 cells were investigated as a function of dye uptake. Cell tracing dyes increase living cell stiffness 3-6 times and cell-to-probe adhesion up to 7 times. These results suggest a more significant effect than toxins, such as Thrombin. A simple analytical model was derived to enable the extraction of the Young’s moduli of the cell membrane and cytoskeleton from the force-deformation profiles measured for individual cells. The increase in Young’s modulus of the membrane is 3-7 times, which is more significant than that of the cytoskeleton (1.1-3.4 times). We propose that changes in cell mechanics upon the addition of fluorescent tracing dye are primarily due to incorporation of amphiphilic dye molecules into the cellular plasma membrane, which increases the lateral interaction among phospholipid chains and thus enhances their rigidity and adhesion.

Regulation of Cell Cytoskeleton and Membrane Mechanics by Electric Field: Role of Linker Proteins

Titushkin, Igor; Cho, Michael
Fonte: The Biophysical Society Publicador: The Biophysical Society
Tipo: Artigo de Revista Científica
Publicado em 21/01/2009 EN
Relevância na Pesquisa
45.9%
Cellular mechanics is known to play an important role in the cell homeostasis including proliferation, motility, and differentiation. Significant variation in the mechanical properties between different cell types suggests that control of the cell metabolism is feasible through manipulation of the cell mechanical parameters using external physical stimuli. We investigated the electrocoupling mechanisms of cellular biomechanics modulation by an electrical stimulation in two mechanically distinct cell types—human mesenchymal stem cells and osteoblasts. Application of a 2 V/cm direct current electric field resulted in approximately a twofold decrease in the cell elasticity and depleted intracellular ATP. Reduction in the ATP level led to inhibition of the linker proteins that are known to physically couple the cell membrane and cytoskeleton. The membrane separation from the cytoskeleton was confirmed by up to a twofold increase in the membrane tether length that was extracted from the cell membrane after an electrical stimulation. In comparison to human mesenchymal stem cells, the membrane-cytoskeleton attachment in osteoblasts was much stronger but, in response to the same electrical stimulation, the membrane detachment from the cytoskeleton was found to be more pronounced. The observed effects mediated by an electric field are cell type- and serum-dependent and can potentially be used for electrically assisted cell manipulation. An in-depth understanding and control of the mechanisms to regulate cell mechanics by external physical stimulus (e.g....

Microfluidics as a functional tool for cell mechanics

Vanapalli, Siva A.; Duits, Michel H. G.; Mugele, Frieder
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
Publicado em 05/01/2009 EN
Relevância na Pesquisa
45.91%
Living cells are a fascinating demonstration of nature’s most intricate and well-coordinated micromechanical objects. They crawl, spread, contract, and relax—thus performing a multitude of complex mechanical functions. Alternatively, they also respond to physical and chemical cues that lead to remodeling of the cytoskeleton. To understand this intricate coupling between mechanical properties, mechanical function and force-induced biochemical signaling requires tools that are capable of both controlling and manipulating the cell microenvironment and measuring the resulting mechanical response. In this review, the power of microfluidics as a functional tool for research in cell mechanics is highlighted. In particular, current literature is discussed to show that microfluidics powered by soft lithographic techniques offers the following capabilities that are of significance for understanding the mechanical behavior of cells: (i) Microfluidics enables the creation of in vitro models of physiological environments in which cell mechanics can be probed. (ii) Microfluidics is an excellent means to deliver physical cues that affect cell mechanics, such as cell shape, fluid flow, substrate topography, and stiffness. (iii) Microfluidics can also expose cells to chemical cues...

The regulatory role of cell mechanics for migration of differentiating myeloid cells

Lautenschläger, Franziska; Paschke, Stephan; Schinkinger, Stefan; Bruel, Arlette; Beil, Michael; Guck, Jochen
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
45.87%
Migration of cells is important for tissue maintenance, immune response, and often altered in disease. While biochemical aspects, including cell adhesion, have been studied in detail, much less is known about the role of the mechanical properties of cells. Previous measurement methods rely on contact with artificial surfaces, which can convolute the results. Here, we used a non-contact, microfluidic optical stretcher to study cell mechanics, isolated from other parameters, in the context of tissue infiltration by acute promyelocytic leukemia (APL) cells, which occurs during differentiation therapy with retinoic acid. Compliance measurements of APL cells reveal a significant softening during differentiation, with the mechanical properties of differentiated cells resembling those of normal neutrophils. To interfere with the migratory ability acquired with the softening, differentiated APL cells were exposed to paclitaxel, which stabilizes microtubules. This treatment does not alter compliance but reduces cell relaxation after cessation of mechanical stress six-fold, congruent with a significant reduction of motility. Our observations imply that the dynamical remodeling of cell shape required for tissue infiltration can be frustrated by stiffening the microtubular system. This link between the cytokeleton...

Atomic force microscopy probing in the measurement of cell mechanics

Kirmizis, Dimitrios; Logothetidis, Stergios
Fonte: Dove Medical Press Publicador: Dove Medical Press
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
45.79%
Atomic force microscope (AFM) has been used incrementally over the last decade in cell biology. Beyond its usefulness in high resolution imaging, AFM also has unique capabilities for probing the viscoelastic properties of living cells in culture and, even more, mapping the spatial distribution of cell mechanical properties, providing thus an indirect indicator of the structure and function of the underlying cytoskeleton and cell organelles. AFM measurements have boosted our understanding of cell mechanics in normal and diseased states and provide future potential in the study of disease pathophysiology and in the establishment of novel diagnostic and treatment options.

Cell Mechanics, Structure, and Function Are Regulated by the Stiffness of the Three-Dimensional Microenvironment

Chen, J.; Irianto, J.; Inamdar, S.; Pravincumar, P.; Lee, D.A.; Bader, D.L.; Knight, M.M.
Fonte: The Biophysical Society Publicador: The Biophysical Society
Tipo: Artigo de Revista Científica
Publicado em 19/09/2012 EN
Relevância na Pesquisa
55.84%
This study adopts a combined computational and experimental approach to determine the mechanical, structural, and metabolic properties of isolated chondrocytes cultured within three-dimensional hydrogels. A series of linear elastic and hyperelastic finite-element models demonstrated that chondrocytes cultured for 24 h in gels for which the relaxation modulus is <5 kPa exhibit a cellular Young’s modulus of ∼5 kPa. This is notably greater than that reported for isolated chondrocytes in suspension. The increase in cell modulus occurs over a 24-h period and is associated with an increase in the organization of the cortical actin cytoskeleton, which is known to regulate cell mechanics. However, there was a reduction in chromatin condensation, suggesting that changes in the nucleus mechanics may not be involved. Comparison of cells in 1% and 3% agarose showed that cells in the stiffer gels rapidly develop a higher Young’s modulus of ∼20 kPa, sixfold greater than that observed in the softer gels. This was associated with higher levels of actin organization and chromatin condensation, but only after 24 h in culture. Further studies revealed that cells in stiffer gels synthesize less extracellular matrix over a 28-day culture period. Hence...

Cellular Pressure and Volume Regulation and Implications for Cell Mechanics

Jiang, Hongyuan; Sun, Sean X.
Fonte: The Biophysical Society Publicador: The Biophysical Society
Tipo: Artigo de Revista Científica
Publicado em 06/08/2013 EN
Relevância na Pesquisa
45.91%
In eukaryotic cells, small changes in cell volume can serve as important signals for cell proliferation, death, and migration. Volume and shape regulation also directly impacts the mechanics of cells and tissues. Here, we develop a mathematical model of cellular volume and pressure regulation, incorporating essential elements such as water permeation, mechanosensitive channels, active ion pumps, and active stresses in the cortex. The model can fully explain recent experimental data, and it predicts cellular volume and pressure for several models of cell cortical mechanics. Moreover, we show that when cells are subjected to an externally applied load, such as in an atomic force microscopy indentation experiment, active regulation of volume and pressure leads to a complex cellular response. Instead of the passive mechanics of the cortex, the observed cell stiffness depends on several factors working together. This provides a mathematical explanation of rate-dependent response of cells under force.

The temperature dependence of cell mechanics measured by atomic force microscopy

Sunyer, R; Trepat, X; Fredberg, J J; Farré, R; Navajas, D
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/07/2009 EN
Relevância na Pesquisa
45.92%
The cytoskeleton is a complex polymer network that regulates the structural stability of living cells. Although the cytoskeleton plays a key role in many important cell functions, the mechanisms that regulate its mechanical behaviour are poorly understood. Potential mechanisms include the entropic elasticity of cytoskeletal filaments, glassy-like inelastic rearrangements of cross-linking proteins and the activity of contractile molecular motors that sets the tensional stress (prestress) borne by the cytoskeleton filaments. The contribution of these mechanisms can be assessed by studying how cell mechanics depends on temperature. The aim of this work was to elucidate the effect of temperature on cell mechanics using atomic force microscopy. We measured the complex shear modulus (G*) of human alveolar epithelial cells over a wide frequency range (0.1–25.6 Hz) at different temperatures (13–37 °C). In addition, we probed cell prestress by mapping the contractile forces that cells exert on the substrate by means of traction microscopy. To assess the role of actomyosin contraction in the temperature-induced changes in G* and cell prestress, we inhibited the Rho kinase pathway of the myosin light chain phosphorylation with Y-27632. Our results show that with increasing temperature...

The Effect of Enterohemorrhagic E. coli Infection on the Cell Mechanics of Host Cells

Chen, Yin-Quan; Su, Pin-Tzu; Chen, Yu-Hsuan; Wei, Ming-Tzo; Huang, Chien-Hsiu; Osterday, Kathryn; del Álamo, Juan C.; Syu, Wan-Jr; Chiou, Arthur
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 04/11/2014 EN
Relevância na Pesquisa
45.79%
Enterohaemorrhagic E. coli (EHEC) is a type of human pathogenic bacteria. The main virulence characteristics of EHEC include the formation of attaching and effacing lesions (A/E lesions) and the production of one or more Shiga-like toxins, which may induce human uremic complications. When EHEC infects host cells, it releases translocated intimin receptor (Tir) and effector proteins inside the host cells, inducing the rearrangement and accumulation of the F-actin cytoskeleton, a phenotype leading to the formation of pedestals in the apical cell surface, and the growth of stress fibers at the base of the cells. To examine the effect of EHEC infection on cell mechanics, we carried out a series of experiments to examine HeLa cells with and without EHEC infection to quantify the changes in (1) focal adhesion area, visualized by anti-vinculin staining; (2) the distribution and orientation of stress fibers; and (3) the intracellular viscoelasticity, via directional video particle tracking microrheology. Our results indicated that in EHEC-infected HeLa cells, the focal adhesion area increased and the actin stress fibers became thicker and more aligned. The cytoskeletal reorganization induced by EHEC infection mediated a dramatic increase in the cytoplasmic elastic shear modulus of the infected cells...

Cell mechanics: principles, practices, and prospects

Moeendarbary, Emad; Harris, Andrew R
Fonte: John Wiley & Sons, Inc. Publicador: John Wiley & Sons, Inc.
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
45.81%
Cells generate and sustain mechanical forces within their environment as part of their normal physiology. They are active materials that can detect mechanical stimulation by the activation of mechanosensitive signaling pathways, and respond to physical cues through cytoskeletal re-organization and force generation. Genetic mutations and pathogens that disrupt the cytoskeletal architecture can result in changes to cell mechanical properties such as elasticity, adhesiveness, and viscosity. On the other hand, perturbations to the mechanical environment can affect cell behavior. These transformations are often a hallmark and symptom of a variety of pathologies. Consequently, there are now a myriad of experimental techniques and theoretical models adapted from soft matter physics and mechanical engineering to characterize cell mechanical properties. Interdisciplinary research combining modern molecular biology with advanced cell mechanical characterization techniques now paves the way for furthering our fundamental understanding of cell mechanics and its role in development, physiology, and disease. We describe a generalized outline for measuring cell mechanical properties including loading protocols, tools, and data interpretation. We summarize recent advances in the field and explain how cell biomechanics research can be adopted by physicists...

Non-contact acoustic radiation force impulse microscopy via photoacoustic detection for probing breast cancer cell mechanics

Hwang, Jae Youn; Kang, Bong Jin; Lee, Changyang; Kim, Hyung Ham; Park, Jinhyoung; Zhou, Qifa; Shung, K. Kirk
Fonte: Optical Society of America Publicador: Optical Society of America
Tipo: Artigo de Revista Científica
Publicado em 03/12/2014 EN
Relevância na Pesquisa
45.88%
We demonstrate a novel non-contact method: acoustic radiation force impulse microscopy via photoacoustic detection (PA-ARFI), capable of probing cell mechanics. A 30 MHz lithium niobate ultrasound transducer is utilized for both detection of phatoacoustic signals and generation of acoustic radiation force. To track cell membrane displacements by acoustic radiation force, functionalized single-walled carbon nanotubes are attached to cell membrane. Using the developed microscopy evaluated with agar phantoms, the mechanics of highly- and weakly-metastatic breast cancer cells are quantified. These results clearly show that the PA-ARFI microscopy may serve as a novel tool to probe mechanics of single breast cancer cells.

High-throughput ballistic injection nanorheology to measure cell mechanics

Wu, Pei-Hsun; Hale, Christopher M; Chen, Wei-Chiang; Lee, Jerry S H; Tseng, Yiider; Wirtz, Denis
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 05/01/2012 EN
Relevância na Pesquisa
45.85%
High-throughput ballistic injection nanorheology is a method for the quantitative study of cell mechanics. Cell mechanics are measured by ballistic injection of submicron particles into the cytoplasm of living cells and tracking the spontaneous displacement of the particles at high spatial resolution. The trajectories of the cytoplasm-embedded particles are transformed into mean-squared displacements, which are subsequently transformed into frequency-dependent viscoelastic moduli and time-dependent creep compliance of the cytoplasm. This method allows for the study of a wide range of cellular conditions, including cells inside a 3D matrix, cell subjected to shear flows and biochemical stimuli, and cells in a live animal. Ballistic injection lasts < 1 min and is followed by overnight incubation. Multiple particle tracking for one cell lasts < 1 min. Forty cells can be examined in < 1 h.

Investigating cell mechanics with atomic force microscopy

Haase, Kristina; Pelling, Andrew E.
Fonte: The Royal Society Publicador: The Royal Society
Tipo: Artigo de Revista Científica
Publicado em 06/03/2015 EN
Relevância na Pesquisa
45.84%
Transmission of mechanical force is crucial for normal cell development and functioning. However, the process of mechanotransduction cannot be studied in isolation from cell mechanics. Thus, in order to understand how cells ‘feel’, we must first understand how they deform and recover from physical perturbations. Owing to its versatility, atomic force microscopy (AFM) has become a popular tool to study intrinsic cellular mechanical properties. Used to directly manipulate and examine whole and subcellular reactions, AFM allows for top-down and reconstitutive approaches to mechanical characterization. These studies show that the responses of cells and their components are complex, and largely depend on the magnitude and time scale of loading. In this review, we generally describe the mechanotransductive process through discussion of well-known mechanosensors. We then focus on discussion of recent examples where AFM is used to specifically probe the elastic and inelastic responses of single cells undergoing deformation. We present a brief overview of classical and current models often used to characterize observed cellular phenomena in response to force. Both simple mechanistic models and complex nonlinear models have been used to describe the observed cellular behaviours...

BE.410J Molecular, Cellular and Tissue Biomechanics, Spring 2003; Molecular, Cellular and Tissue Biomechanics

Kamm, Roger D.; Grodzinsky, Alan J.; Doyle, Patrick S.; Jonas, Maxine
Fonte: MIT - Massachusetts Institute of Technology Publicador: MIT - Massachusetts Institute of Technology
EN-US
Relevância na Pesquisa
45.91%
This course develops and applies scaling laws and the methods of continuum mechanics to biomechanical phenomena over a range of length scales. Topics include: structure of tissues and the molecular basis for macroscopic properties; chemical and electrical effects on mechanical behavior; cell mechanics, motility and adhesion; biomembranes; biomolecular mechanics and molecular motors. Experimental methods for probing structures at the tissue, cellular, and molecular levels.

Multicellular Architecture of Malignant Breast Epithelia Influences Mechanics

Venugopalan, Gautham; Camarillo, David B.; Webster, Kevin D.; Reber, Clay D.; Sethian, James A.; Weaver, Valerie M.; Fletcher, Daniel A.; El-Samad, Hana; Rycroft, Chris H.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
45.88%
Cell–matrix and cell–cell mechanosensing are important in many cellular processes, particularly for epithelial cells. A crucial question, which remains unexplored, is how the mechanical microenvironment is altered as a result of changes to multicellular tissue structure during cancer progression. In this study, we investigated the influence of the multicellular tissue architecture on mechanical properties of the epithelial component of the mammary acinus. Using creep compression tests on multicellular breast epithelial structures, we found that pre-malignant acini with no lumen (MCF10AT) were significantly stiffer than normal hollow acini (MCF10A) by 60%. This difference depended on structural changes in the pre-malignant acini, as neither single cells nor normal multicellular acini tested before lumen formation exhibited these differences. To understand these differences, we simulated the deformation of the acini with different multicellular architectures and calculated their mechanical properties; our results suggest that lumen filling alone can explain the experimentally observed stiffness increase. We also simulated a single contracting cell in different multicellular architectures and found that lumen filling led to a 20% increase in the “perceived stiffness” of a single contracting cell independent of any changes to matrix mechanics. Our results suggest that lumen filling in carcinogenesis alters the mechanical microenvironment in multicellular epithelial structures...

14-3-3, an integrator of cell mechanics and cytokinesis

Robinson, Douglas N
Fonte: Landes Bioscience Publicador: Landes Bioscience
Tipo: Artigo de Revista Científica
Publicado em //2010 EN
Relevância na Pesquisa
45.77%
One of the goals of understanding cytokinesis is to uncover the molecular regulation of the cellular mechanical properties that drive cell shape change. Such regulatory pathways are likely to be used at multiple stages of a cell's life, but are highly featured during cell division. Recently, we demonstrated that 14-3-3 (encoded by a single gene in the social amoeba Dictyostelium discoideum) serves to integrate key cytoskeletal components—microtubules, Rac and myosin II—to control cell mechanics and cytokinesis. As 14-3-3 proteins are frequently altered in a variety of human tumors, we extend these observations to suggest possible additional roles for how 14-3-3 proteins may contribute to tumorigenesis.

Modulation of host cell mechanics by Trypanosoma cruzi

Mott, Adam; Lenormand, Guillaume; Costales, Jaime; Fredberg, Jeffrey J.; Burleigh, Barbara A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/2009 EN
Relevância na Pesquisa
45.75%
To investigate the effects of Trypanosoma cruzi on the mechanical properties of infected host cells, cytoskeletal stiffness and remodeling dynamics were measured in parasite-infected fibroblasts. We find that cell stiffness decreases in a time-dependent fashion in T. cruzi-infected human foreskin fibroblasts without a significant change in the dynamics of cytoskeletal remodeling. In contrast, cells exposed to T. cruzi secreted/released components become significantly stiffer within two hours of exposure and exhibit increased remodeling dynamics. These findings represent the first direct mechanical data to suggest a physical picture in which an intact, stiff, and rapidly remodeling cytoskeleton facilitates early stages of T. cruzi invasion and parasite retention, followed by subsequent softening and disassembly of the cytoskeleton to accommodate intracellular replication of parasites. We further suggest that these changes occur through protein kinase A and inhibition of the Rho/Rho kinase signaling pathway. In the context of tissue infection, changes in host cell mechanics could adversely affect the function of the infected organs, and may play an important role on the pathophysiology of Chagas' disease.

Active Tension Network model of epithelial mechanics

Noll, Nicholas; Mani, Madhav; Heemskerk, Idse; Streichan, Sebastian; Shraiman, Boris I.
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 03/08/2015
Relevância na Pesquisa
45.84%
It is now widely recognized that mechanical interactions between cells play a crucial role in epithelial morphogenesis, yet understanding the mechanisms through which stress and deformation affect cell behavior remains an open problem due to the complexity inherent in the mechanical behavior of cells and the difficulty of direct measurement of forces within tissues. Theoretical models can help by focusing experimental studies and by providing the framework for interpreting measurements. To that end, "vertex models" have introduced an approximation of epithelial cell mechanics based on a polygonal tiling representation of planar tissue. Here we formulate and analyze an Active Tension Network (ATN) model, which is based on the same polygonal representation of epithelial tissue geometry, but in addition i) assumes that mechanical balance is dominated by cortical tension and ii) introduces tension dependent local remodeling of the cortex, representing the active nature of cytoskeletal mechanics. The tension-dominance assumption has immediate implications for the geometry of cells, which we demonstrate to hold in certain types of Drosophila epithelial tissues. We demonstrate that stationary configurations of an ATN form a manifold with one degree of freedom per cell...