Core 2 Abstract Theory Core: Multiscale models for mechano-chemical phenomena in liver cancer Provide an abstract/summary for the proposed Shared Resource Core, including which Research Projects will be supported by the Core. The three members of the theoretical physics core will support all three projects with theory and computation. Radhakrishnan uses computational chemistry to develop models at the molecular scale and then multiscale modeling algorithms to explore molecular effects at larger scales. Shenoy conducts discrete finite element calculations and coarse-grains to develop continuum models for the elastic and viscous response of the extracellular matrix (ECM) and the interaction between cells and the ECM. Liu uses analytical theory and computation to construct and study continuum models of active matter that apply at scales ranging from the cellular to the tissue level. Cells respond to mechanical stresses in their environment via a complex interplay between mechanics and biochemistry. Each of the three projects proposed for PSoC@Penn addresses this interplay. Project 1 addresses the effect of increased liver tissue stiffness on the malignant transformation of hepatocytes. Theoretical support for this project (Core-2/Aim-1) will focus on understanding the physical mechanisms underlying the causal relation between mechanical changes to the liver and the development of HCC. Project 2 advocates and tests a provocative hypothesis for mechano-transduction of the effect of the physical microenvironment in hepatocellular carcinoma (HCC) on the altered specificity of subcellular signals in hepatocytes and stromal cells, and its consequences for cell fate.
Aim 2 of Core-2 interfaces directly with Project 2, which is model-driven with bidirectional coupling and iterative feedback between theory and experiment. Project 3 investigates the hypothesis that dysregulation of nuclear structure proteins contributes to disease. Core-2/Aim-3(a), which focuses on cell migration through pores and the extracellular matrix, is directly tied to Project-3/Aim-2. Core-2/Aim-3(b) focuses on DNA repair, also addressed experimentally in Project-3/Aim-2. The theory core will be held together via close collaboration among the theorists, and will be integrated into all three projects via collaboration with team members. The role of the core will not only be to provide theoretical support in analyzing and interpreting experimental data, but also to develop ideas in tandem with other members of PSoC@Penn to shape directions of inquiry as the project progresses. 22

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
United States
Zip Code
Ramakrishnan, N; Sreeja, K K; Roychoudhury, Arpita et al. (2018) Excess area dependent scaling behavior of nano-sized membrane tethers. Phys Biol 15:026002
Lee, Calvin K; de Anda, Jaime; Baker, Amy E et al. (2018) Multigenerational memory and adaptive adhesion in early bacterial biofilm communities. Proc Natl Acad Sci U S A 115:4471-4476
Nair, Praful R; Alvey, Cory; Jin, Xiaoling et al. (2018) Filomicelles Deliver a Chemo-Differentiation Combination of Paclitaxel and Retinoic Acid That Durably Represses Carcinomas in Liver to Prolong Survival. Bioconjug Chem 29:914-927
Huang, Mo; Wang, Jingshu; Torre, Eduardo et al. (2018) SAVER: gene expression recovery for single-cell RNA sequencing. Nat Methods 15:539-542
Ban, Ehsan; Franklin, J Matthew; Nam, Sungmin et al. (2018) Mechanisms of Plastic Deformation in Collagen Networks Induced by Cellular Forces. Biophys J 114:450-461
Smith, Lucas R; Cho, Sangkyun; Discher, Dennis E (2018) Stem Cell Differentiation is Regulated by Extracellular Matrix Mechanics. Physiology (Bethesda) 33:16-25
Holle, Andrew W; Young, Jennifer L; Van Vliet, Krystyn J et al. (2018) Cell-Extracellular Matrix Mechanobiology: Forceful Tools and Emerging Needs for Basic and Translational Research. Nano Lett 18:1-8
Pfeifer, Charlotte R; Xia, Yuntao; Zhu, Kuangzheng et al. (2018) Constricted migration increases DNA damage and independently represses cell cycle. Mol Biol Cell 29:1948-1962
Xia, Yuntao; Ivanovska, Irena L; Zhu, Kuangzheng et al. (2018) Nuclear rupture at sites of high curvature compromises retention of DNA repair factors. J Cell Biol 217:3796-3808
Ramakrishnan, N; Bradley, Ryan P; Tourdot, Richard W et al. (2018) Biophysics of membrane curvature remodeling at molecular and mesoscopic lengthscales. J Phys Condens Matter 30:273001

Showing the most recent 10 out of 68 publications