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Dive into the research topics where Heather A. Cirka is active.

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Featured researches published by Heather A. Cirka.


Biophysical Journal | 2013

Nonlinear strain stiffening is not sufficient to explain how far cells can feel on fibrous protein gels.

Mathilda S. Rudnicki; Heather A. Cirka; Maziar Aghvami; Edward A. Sander; Qi Wen; Kristen L. Billiar

Recent observations suggest that cells on fibrous extracellular matrix materials sense mechanical signals over much larger distances than they do on linearly elastic synthetic materials. In this work, we systematically investigate the distance fibroblasts can sense a rigid boundary through fibrous gels by quantifying the spread areas of human lung fibroblasts and 3T3 fibroblasts cultured on sloped collagen and fibrin gels. The cell areas gradually decrease as gel thickness increases from 0 to 150 μm, with characteristic sensing distances of >65 μm below fibrin and collagen gels, and spreading affected on gels as thick as 150 μm. These results demonstrate that fibroblasts sense deeper into collagen and fibrin gels than they do into polyacrylamide gels, with the latter exhibiting characteristic sensing distances of <5 μm. We apply finite-element analysis to explore the role of strain stiffening, a characteristic mechanical property of collagen and fibrin that is not observed in polyacrylamide, in facilitating mechanosensing over long distances. Our analysis shows that the effective stiffness of both linear and nonlinear materials sharply increases once the thickness is reduced below 5 μm, with only a slight enhancement in sensitivity to depth for the nonlinear material at very low thickness and high applied traction. Multiscale simulations with a simplified geometry predict changes in fiber alignment deep into the gel and a large increase in effective stiffness with a decrease in substrate thickness that is not predicted by nonlinear elasticity. These results suggest that the observed cell-spreading response to gel thickness is not explained by the nonlinear strain-stiffening behavior of the material alone and is likely due to the fibrous nature of the proteins.


EMBO Reports | 2017

TRIP6 inhibits Hippo signaling in response to tension at adherens junctions

Shubham Dutta; Sebastian Mana-Capelli; Murugan Paramasivam; Ishani Dasgupta; Heather A. Cirka; Kris Billiar; Dannel McCollum

The transcriptional co‐activator YAP controls cell proliferation, survival, and tissue regeneration in response to changes in the mechanical environment. It is not known how mechanical stimuli such as tension are sensed and how the signal is transduced to control YAP activity. Here, we show that the LIM domain protein TRIP6 acts as part of a mechanotransduction pathway at adherens junctions to promote YAP activity by inhibiting the LATS1/2 kinases. Previous studies showed that vinculin at adherens junctions becomes activated by mechanical tension. We show that vinculin inhibits Hippo signaling by recruiting TRIP6 to adherens junctions and stimulating its binding to and inhibition of LATS1/2 in response to tension. TRIP6 competes with MOB1 for binding to LATS1/2 thereby blocking MOB1 from recruiting the LATS1/2 activating kinases MST1/2. Together, these findings reveal a novel pathway that responds to tension at adherens junctions to control Hippo pathway signaling.


bioRxiv | 2017

TRIP6 inhibits the Hippo signaling pathway in response to tension at adherens junctions

Shubham Dutta; Sebastian Mana-Capelli; Murugan Paramasivam; Ishani Dasgupta; Heather A. Cirka; Kris Billiar; Dannel McCollum

The transcriptional co-activator YAP controls cell proliferation, survival, and tissue regeneration in response to changes in the mechanical environment. It is not known how mechanical stimuli such as tension are sensed and how the signal is transduced to control YAP activity. Here we show that the LIM domain protein TRIP6 acts as part of a mechanotransduction pathway at adherens junctions to promote YAP activity by inhibiting the LATS1/2 kinases. Previous studies showed that vinculin at adherens junctions becomes activated by mechanical tension. We show that vinculin inhibits Hippo signaling by recruiting TRIP6 to adherens junctions and stimulating its binding to and inhibition of LATS1/2 in response to tension. TRIP6 competes with MOB1 for binding to LATS1/2 thereby blocking MOB1 from recruiting the LATS1/2 activating kinases MST1/2. Together these findings reveal a novel mechanotransduction cascade that transduces tension signals sensed at adherens junctions to control Hippo pathway signaling.


ASME 2011 Summer Bioengineering Conference, Parts A and B | 2011

Extending Standard Rotational Rheometry for Small, Irregular, Anisotropic Tissues and Gels

Heather A. Cirka; William W. Farr; Stephan A. Koehler; Kristen L. Billiar

Quantification of the viscoelastic properties of soft tissues and protein gels is vital to the understanding of normal tissue development and disease progression and for evaluating the cell-mediated remodeling of fibrous protein-based engineered tissues (e.g., collagen, fibrin). Rotational (shear) rheometers are theoretically well suited for characterizing the storage and loss modulus of such soft gels; however, standard “geometries” used in such devices require relatively large, homogeneous samples to generate sufficient torque for accurate analysis of very soft materials, and the analysis generally assumes linear isotropic viscoelastic behavior. Newly formed tissues and biological protein gels such as blood clots are often small, soft (low stiffness), irregularly shaped, anisotropic, and difficult to handle. The aim of this work is to develop a method that will allow the accurate characterization of small, irregular protein gels utilizing an industry-standard rheometer.Copyright


Annals of Biomedical Engineering | 2012

Eccentric Rheometry for Viscoelastic Characterization of Small, Soft, Anisotropic, and Irregularly Shaped Biopolymer Gels and Tissue Biopsies

Heather A. Cirka; Stephan A. Koehler; William W. Farr; Kristen L. Billiar


Lab on a Chip | 2017

Reproducible in vitro model for dystrophic calcification of cardiac valvular interstitial cells: insights into the mechanisms of calcific aortic valvular disease

Heather A. Cirka; Johana Uribe; Vivian Liang; Frederick J. Schoen; Kristen L. Billiar


Biophysical Journal | 2016

Active Traction Force Response to Long-Term Cyclic Stretch Is Dependent on Cell Pre-stress

Heather A. Cirka; Melissa Monterosso; Nicole Diamantides; John T. Favreau; Qi Wen; Kristen L. Billiar


Journal of Long-term Effects of Medical Implants | 2015

Mechanoregulation of aortic valvular interstitial cell life and death.

Heather A. Cirka; Mehmet H. Kural; Kristen L. Billiar


Archive | 2016

Geometric Control of YAP-dependent Mechanotransduction: A Proposed Model

Ngozi A. Eze; Heather A. Cirka; Kristen L. Billiar


Archive | 2012

METHODS AND SYSTEMS FOR VISCOELASTIC CHARACTERIZATION OF IRREGULARLY SHAPED ANISOTROPIC BIOLOGICAL SAMPLES

Heather A. Cirka; Kristen L. Billiar

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Kristen L. Billiar

Worcester Polytechnic Institute

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William W. Farr

Worcester Polytechnic Institute

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Dannel McCollum

University of Massachusetts Medical School

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Ishani Dasgupta

University of Massachusetts Medical School

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Kris Billiar

Worcester Polytechnic Institute

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Murugan Paramasivam

University of Massachusetts Medical School

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Qi Wen

Worcester Polytechnic Institute

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Sebastian Mana-Capelli

University of Massachusetts Medical School

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Shubham Dutta

University of Massachusetts Medical School

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