A data-driven approach to modeling cancer cell mechanics during microcirculatory transport
Abstract
In order to understand the effect of cellular level features on the transport of circulating cancer cells in the microcirculation, there has been an increasing reliance on high-resolution in silico models. Accurate simulation of cancer cells flowing with blood cells requires resolving cellular-scale interactions in 3D, which is a significant computational undertaking warranting a cancer cell model that is both computationally efficient yet sufficiently complex to capture relevant behavior. Given that the characteristics of metastatic spread are known to depend on cancer type, it is crucial to account for mechanistic behavior representative of a specific cancer’s cells. To address this gap, in the present work we develop and validate a means by which an efficient and popular membrane model-based approach can be used to simulate deformable cancer cells and reproduce experimental data from specific cell lines. Here, cells are modeled using the immersed boundary method (IBM) within a lattice Boltzmann method (LBM) fluid solver, and the finite element method (FEM) is used to model cell membrane resistance to deformation. Through detailed comparisons with experiments, we (i) validate this model to represent cancer cells undergoing large deformation, (ii) outline a systematic approach to parameterize different cell lines to optimally fit experimentalmore »
- Authors:
-
- Duke Univ., Durham, NC (United States)
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Publication Date:
- Research Org.:
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE Laboratory Directed Research and Development (LDRD) Program; National Institutes of Health (NIH); National Science Foundation (NSF)
- OSTI Identifier:
- 1813242
- Grant/Contract Number:
- AC05-00OR22725; U01-CA253511; 1943036
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Scientific Reports
- Additional Journal Information:
- Journal Volume: 11; Journal Issue: 1; Journal ID: ISSN 2045-2322
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Balogh, Peter, Gounley, John, Roychowdhury, Sayan, and Randles, Amanda. A data-driven approach to modeling cancer cell mechanics during microcirculatory transport. United States: N. p., 2021.
Web. doi:10.1038/s41598-021-94445-5.
Balogh, Peter, Gounley, John, Roychowdhury, Sayan, & Randles, Amanda. A data-driven approach to modeling cancer cell mechanics during microcirculatory transport. United States. https://doi.org/10.1038/s41598-021-94445-5
Balogh, Peter, Gounley, John, Roychowdhury, Sayan, and Randles, Amanda. Tue .
"A data-driven approach to modeling cancer cell mechanics during microcirculatory transport". United States. https://doi.org/10.1038/s41598-021-94445-5. https://www.osti.gov/servlets/purl/1813242.
@article{osti_1813242,
title = {A data-driven approach to modeling cancer cell mechanics during microcirculatory transport},
author = {Balogh, Peter and Gounley, John and Roychowdhury, Sayan and Randles, Amanda},
abstractNote = {In order to understand the effect of cellular level features on the transport of circulating cancer cells in the microcirculation, there has been an increasing reliance on high-resolution in silico models. Accurate simulation of cancer cells flowing with blood cells requires resolving cellular-scale interactions in 3D, which is a significant computational undertaking warranting a cancer cell model that is both computationally efficient yet sufficiently complex to capture relevant behavior. Given that the characteristics of metastatic spread are known to depend on cancer type, it is crucial to account for mechanistic behavior representative of a specific cancer’s cells. To address this gap, in the present work we develop and validate a means by which an efficient and popular membrane model-based approach can be used to simulate deformable cancer cells and reproduce experimental data from specific cell lines. Here, cells are modeled using the immersed boundary method (IBM) within a lattice Boltzmann method (LBM) fluid solver, and the finite element method (FEM) is used to model cell membrane resistance to deformation. Through detailed comparisons with experiments, we (i) validate this model to represent cancer cells undergoing large deformation, (ii) outline a systematic approach to parameterize different cell lines to optimally fit experimental data over a range of deformations, and (iii) provide new insight into nucleated vs. non-nucleated cell models and their ability to match experiments. While many works have used the membrane-model based method employed here to model generic cancer cells, no quantitative comparisons with experiments exist in the literature for specific cell lines undergoing large deformation. Here, we describe a phenomenological, data-driven approach that can not only yield good agreement for large deformations, but explicitly detail how it can be used to represent different cancer cell lines. This model is readily incorporated into cell-resolved hemodynamic transport simulations, and thus offers significant potential to complement experiments towards providing new insights into various aspects of cancer progression.},
doi = {10.1038/s41598-021-94445-5},
journal = {Scientific Reports},
number = 1,
volume = 11,
place = {United States},
year = {Tue Jul 27 00:00:00 EDT 2021},
month = {Tue Jul 27 00:00:00 EDT 2021}
}
Works referenced in this record:
Bending energy of vesicle membranes: General expressions for the first, second, and third variation of the shape energy and applications to spheres and cylinders
journal, May 1989
- Zhong-can, Ou-Yang; Helfrich, Wolfgang
- Physical Review A, Vol. 39, Issue 10
Dynamics of nonspherical compound capsules in simple shear flow
journal, October 2016
- Luo, Zheng Yuan; Bai, Bo Feng
- Physics of Fluids, Vol. 28, Issue 10
Nuclear mechanics during cell migration
journal, February 2011
- Friedl, Peter; Wolf, Katarina; Lammerding, Jan
- Current Opinion in Cell Biology, Vol. 23, Issue 1
The Role of Passive Transbilayer Drug Movement in Multidrug Resistance and Its Modulation
journal, May 1996
- Eytan, Gera D.; Regev, Ronit; Oren, Galit
- Journal of Biological Chemistry, Vol. 271, Issue 22
The multiple facets of drug resistance: one history, different approaches
journal, April 2014
- Niero, Evandro Luís; Rocha-Sales, Bianca; Lauand, Camila
- Journal of Experimental & Clinical Cancer Research, Vol. 33, Issue 1
Entry effects of droplet in a micro confinement: Implications for deformation-based circulating tumor cell microfiltration
journal, March 2015
- Zhang, Zhifeng; Chen, Xiaolin; Xu, Jie
- Biomicrofluidics, Vol. 9, Issue 2
Proposed Spring Network Cell Model Based on a Minimum Energy Concept
journal, January 2010
- Ujihara, Yoshihiro; Nakamura, Masanori; Miyazaki, Hiroshi
- Annals of Biomedical Engineering, Vol. 38, Issue 4
Intracellular Fluid Mechanics: Coupling Cytoplasmic Flow with Active Cytoskeletal Gel
journal, January 2018
- Mogilner, Alex; Manhart, Angelika
- Annual Review of Fluid Mechanics, Vol. 50, Issue 1
Modeling cell entry into a micro-channel
journal, November 2010
- Leong, Fong Yew; Li, Qingsen; Lim, Chwee Teck
- Biomechanics and Modeling in Mechanobiology, Vol. 10, Issue 5
Numerical analysis of blood flow in the heart
journal, November 1977
- Peskin, Charles S.
- Journal of Computational Physics, Vol. 25, Issue 3
Apparent viscosity and cortical tension of blood granulocytes determined by micropipet aspiration
journal, July 1989
- Evans, E.; Yeung, A.
- Biophysical Journal, Vol. 56, Issue 1
Mechanical models for living cells—a review
journal, January 2006
- Lim, C. T.; Zhou, E. H.; Quek, S. T.
- Journal of Biomechanics, Vol. 39, Issue 2
Hemodynamic and morphological characteristics of a growing cerebral aneurysm
journal, July 2019
- Dabagh, Mahsa; Nair, Priya; Gounley, John
- Neurosurgical Focus, Vol. 47, Issue 1
Subdivision surfaces: a new paradigm for thin-shell finite-element analysis
journal, April 2000
- Cirak, Fehmi; Ortiz, Michael; Schr�der, Peter
- International Journal for Numerical Methods in Engineering, Vol. 47, Issue 12
Physical limits of cell migration: Control by ECM space and nuclear deformation and tuning by proteolysis and traction force
journal, June 2013
- Wolf, Katarina; te Lindert, Mariska; Krause, Marina
- Journal of Cell Biology, Vol. 201, Issue 7
Time-dependent particle migration and margination in the pressure-driven channel flow of blood
journal, March 2018
- Qi, Qin M.; Shaqfeh, Eric S. G.
- Physical Review Fluids, Vol. 3, Issue 3
Massively parallel models of the human circulatory system
conference, November 2015
- Randles, Amanda; Draeger, Erik W.; Oppelstrup, Tomas
- SC15: The International Conference for High Performance Computing, Networking, Storage and Analysis, Proceedings of the International Conference for High Performance Computing, Networking, Storage and Analysis
Deciphering the relative contribution of vascular inflammation and blood rheology in metastatic spreading
journal, July 2018
- Mollica, Hilaria; Coclite, Alessandro; Miali, Marco E.
- Biomicrofluidics, Vol. 12, Issue 4
Probing eukaryotic cell mechanics via mesoscopic simulations
journal, September 2017
- Lykov, Kirill; Nematbakhsh, Yasaman; Shang, Menglin
- PLOS Computational Biology, Vol. 13, Issue 9
Unraveling the Vascular Fate of Deformable Circulating Tumor Cells Via a Hierarchical Computational Model
journal, July 2019
- Lenarda, Pietro; Coclite, Alessandro; Decuzzi, Paolo
- Cellular and Molecular Bioengineering, Vol. 12, Issue 6
A computational approach to modeling cellular-scale blood flow in complex geometry
journal, April 2017
- Balogh, Peter; Bagchi, Prosenjit
- Journal of Computational Physics, Vol. 334
Role of deformable cancer cells on wall shear stress-associated-VEGF secretion by endothelium in microvasculature
journal, February 2019
- Dabagh, Mahsa; Randles, Amanda
- PLOS ONE, Vol. 14, Issue 2
A physical sciences network characterization of circulating tumor cell aggregate transport
journal, May 2015
- King, Michael R.; Phillips, Kevin G.; Mitrugno, Annachiara
- American Journal of Physiology-Cell Physiology, Vol. 308, Issue 10
Cortical shell-liquid core model for passive flow of liquid-like spherical cells into micropipets
journal, July 1989
- Yeung, A.; Evans, E.
- Biophysical Journal, Vol. 56, Issue 1
Biomechanical analysis of actin cytoskeleton function based on a spring network cell model
journal, October 2016
- Ghaffari, Hamed; Saidi, Mohammad Said; Firoozabadi, Bahar
- Proceedings of the Institution of Mechanical Engineers, Part C: Journal of Mechanical Engineering Science, Vol. 231, Issue 7
Hydrodynamics of a compound drop with application to leukocyte modeling
journal, April 1998
- Kan, Heng-Chuan; Udaykumar, H. S.; Shyy, Wei
- Physics of Fluids, Vol. 10, Issue 4
Time-dependent recovery of passive neutrophils after large deformation
journal, October 1991
- Tran-Son-Tay, R.; Needham, D.; Yeung, A.
- Biophysical Journal, Vol. 60, Issue 4
Lipids as a Target for Drugs Modulating Multidrug Resistance of Cancer Cells
journal, January 2003
- Hendrich, A.; Michalak, K.
- Current Drug Targets, Vol. 4, Issue 1
Metastatic progression of breast cancer: insights from 50 years of autopsies
journal, December 2013
- Cummings, Margaret C.; Simpson, Peter T.; Reid, Lynne E.
- The Journal of Pathology, Vol. 232, Issue 1
Contribution of the nucleus to the mechanical properties of endothelial cells
journal, February 2002
- Caille, Nathalie; Thoumine, Olivier; Tardy, Yanik
- Journal of Biomechanics, Vol. 35, Issue 2
Towards a regional approach to cell mechanics
journal, April 2004
- Heidemann, Steven R.; Wirtz, Denis
- Trends in Cell Biology, Vol. 14, Issue 4
Deterministic microfluidic ratchet based on the deformation of individual cells
journal, May 2011
- Guo, Quan; McFaul, Sarah M.; Ma, Hongshen
- Physical Review E, Vol. 83, Issue 5
Coupling of finite element and boundary integral methods for a capsule in a Stokes flow: NUMERICAL METHODS FOR A CAPSULE IN A STOKES FLOW
journal, March 2010
- Walter, J.; Salsac, A. -V.; Barthès-Biesel, D.
- International Journal for Numerical Methods in Engineering, Vol. 83, Issue 7
The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber
journal, September 2004
- Dahl, Kris Noel; Kahn, Samuel M.; Wilson, Katherine L.
- Journal of Cell Science, Vol. 117, Issue 20
Capture of microparticles by bolus flow of red blood cells in capillaries
journal, July 2017
- Takeishi, Naoki; Imai, Yohsuke
- Scientific Reports, Vol. 7, Issue 1
Changes in the mechanical properties of fibroblasts during spreading: a micromanipulation study
journal, March 1999
- Thoumine, O.; Cardoso, Olivier; Meister, Jean-Jacques
- European Biophysics Journal, Vol. 28, Issue 3
Deformability-based circulating tumor cell separation with conical-shaped microfilters: Concept, optimization, and design criteria
journal, May 2015
- Aghaamoo, Mohammad; Zhang, Zhifeng; Chen, Xiaolin
- Biomicrofluidics, Vol. 9, Issue 3
The flow of red blood cells through a narrow spleen-like slit
journal, November 2013
- Freund, Jonathan B.
- Physics of Fluids, Vol. 25, Issue 11
Flow of a circulating tumor cell and red blood cells in microvessels
journal, December 2015
- Takeishi, Naoki; Imai, Yohsuke; Yamaguchi, Takami
- Physical Review E, Vol. 92, Issue 6
Isogeometric FEM-BEM simulations of drop, capsule and vesicle dynamics in Stokes flow
journal, August 2017
- Boedec, Gwenn; Leonetti, Marc; Jaeger, Marc
- Journal of Computational Physics, Vol. 342
Immersed Boundary Methods
journal, January 2005
- Mittal, Rajat; Iaccarino, Gianluca
- Annual Review of Fluid Mechanics, Vol. 37, Issue 1
Effect of bending stiffness on the deformation of liquid capsules enclosed by thin shells in shear flow
journal, July 2010
- Le, Duc Vinh
- Physical Review E, Vol. 82, Issue 1
Mechanical stability of the cell nucleus – roles played by the cytoskeleton in nuclear deformation and strain recovery
journal, May 2018
- Wang, Xian; Liu, Haijiao; Zhu, Min
- Journal of Cell Science, Vol. 131, Issue 13
An Adaptive, Cartesian, Front-Tracking Method for the Motion, Deformation and Adhesion of Circulating Cells
journal, July 1998
- Agresar, G.; Linderman, J. J.; Tryggvason, G.
- Journal of Computational Physics, Vol. 143, Issue 2
Cell adhesion during bullet motion in capillaries
journal, August 2016
- Takeishi, Naoki; Imai, Yohsuke; Ishida, Shunichi
- American Journal of Physiology-Heart and Circulatory Physiology, Vol. 311, Issue 2
Cytoplasmic Flow and Mixing Due to Deformation of Motile Cells
journal, November 2017
- Koslover, Elena F.; Chan, Caleb K.; Theriot, Julie A.
- Biophysical Journal, Vol. 113, Issue 9
Strain Energy Function of Red Blood Cell Membranes
journal, March 1973
- Skalak, R.; Tozeren, A.; Zarda, R. P.
- Biophysical Journal, Vol. 13, Issue 3
Microfluidic micropipette aspiration for measuring the deformability of single cells
journal, January 2012
- Guo, Quan; Park, Sunyoung; Ma, Hongshen
- Lab on a Chip, Vol. 12, Issue 15
Characterizing deformability and surface friction of cancer cells
journal, April 2013
- Byun, S.; Son, S.; Amodei, D.
- Proceedings of the National Academy of Sciences, Vol. 110, Issue 19
Two-dimensional Finite Element Model of Breast Cancer Cell Motion Through a Microfluidic Channel
journal, January 2019
- Barber, Jared; Zhu, Luoding
- Bulletin of Mathematical Biology, Vol. 81, Issue 4
In Situ Mechanical Characterization of the Cell Nucleus by Atomic Force Microscopy
journal, April 2014
- Liu, Haijiao; Wen, Jun; Xiao, Yun
- ACS Nano, Vol. 8, Issue 4
Multi-GPU immersed boundary method hemodynamics simulations
journal, July 2020
- Ames, Jeff; Puleri, Daniel F.; Balogh, Peter
- Journal of Computational Science, Vol. 44
Optofluidic real-time cell sorter for longitudinal CTC studies in mouse models of cancer
journal, January 2019
- Hamza, Bashar; Ng, Sheng Rong; Prakadan, Sanjay M.
- Proceedings of the National Academy of Sciences, Vol. 116, Issue 6
Dynamics phenotyping across length and time scales in collective cell migration
journal, September 2019
- Lee, Rachel M.; Losert, Wolfgang
- Seminars in Cell & Developmental Biology, Vol. 93
The Expression of Three Genes in Primary Non–Small Cell Lung Cancer Is Associated with Metastatic Spread to the Brain
journal, February 2009
- Grinberg-Rashi, Helena; Ofek, Efrat; Perelman, Marina
- Clinical Cancer Research, Vol. 15, Issue 5
Numerical simulation of a compound capsule in a constricted microchannel
journal, January 2017
- Gounley, John; Draeger, Erik W.; Randles, Amanda
- Procedia Computer Science, Vol. 108
Deformation of spherical compound capsules in simple shear flow
journal, June 2015
- Luo, Zheng Yuan; He, Long; Bai, Bo Feng
- Journal of Fluid Mechanics, Vol. 775
Rapid Flow of Passive Neutrophils Into a 4 μm Pipet and Measurement of Cytoplasmic Viscosity
journal, August 1990
- Needham, D.; Hochmuth, R. M.
- Journal of Biomechanical Engineering, Vol. 112, Issue 3
Clusters of circulating tumor cells traverse capillary-sized vessels
journal, April 2016
- Au, Sam H.; Storey, Brian D.; Moore, John C.
- Proceedings of the National Academy of Sciences, Vol. 113, Issue 18
Computing the ankle-brachial index with parallel computational fluid dynamics
journal, January 2019
- Gounley, John; Draeger, Erik W.; Oppelstrup, Tomas
- Journal of Biomechanics, Vol. 82
An immersed boundary framework for modelling the growth of individual cells: An application to the early tumour development
journal, July 2007
- Rejniak, Katarzyna A.
- Journal of Theoretical Biology, Vol. 247, Issue 1
Cell membrane modulation as adjuvant in cancer therapy
journal, January 2017
- Zalba, Sara; ten Hagen, Timo L. M.
- Cancer Treatment Reviews, Vol. 52
Leukocyte relaxation properties
journal, August 1988
- Sung, K. L.; Dong, C.; Schmid-Schönbein, G. W.
- Biophysical Journal, Vol. 54, Issue 2
Trends in primary liver cancer
journal, January 1998
- Deuffic, Sylvie; Poynard, Thierry; Buffat, Laurent
- The Lancet, Vol. 351, Issue 9097
Passive mechanical behavior of human neutrophils: power-law fluid
journal, November 1993
- Tsai, M. A.; Frank, R. S.; Waugh, R. E.
- Biophysical Journal, Vol. 65, Issue 5
Lattice Boltzmann Method for Fluid Flows
journal, January 1998
- Chen, Shiyi; Doolen, Gary D.
- Annual Review of Fluid Mechanics, Vol. 30, Issue 1
Collective cell migration over long time scales reveals distinct phenotypes
journal, May 2016
- Lee, R. M.; Stuelten, C. H.; Parent, C. A.
- Convergent Science Physical Oncology, Vol. 2, Issue 2
Numerical simulation of a single cell passing through a narrow slit
journal, April 2016
- Xiao, L. L.; Liu, Y.; Chen, S.
- Biomechanics and Modeling in Mechanobiology, Vol. 15, Issue 6
Biomechanics and biophysics of cancer cells☆
journal, July 2007
- Suresh, S.
- Acta Biomaterialia, Vol. 3, Issue 4
Effect of constitutive laws for two-dimensional membranes on flow-induced capsule deformation
journal, June 2002
- BarthÈS-Biesel, Dominique; Diaz, Anna; Dhenin, Emmanuelle
- Journal of Fluid Mechanics, Vol. 460
Strain Hardening of Actin Filament Networks
journal, November 2000
- Xu, Jingyuan; Tseng, Yiider; Wirtz, Denis
- Journal of Biological Chemistry, Vol. 275, Issue 46
The Extracellular, Cellular, and Nuclear Stiffness, a Trinity in the Cancer Resistome—A Review
journal, December 2019
- Deville, Sara Sofia; Cordes, Nils
- Frontiers in Oncology, Vol. 9
Lung metastasis genes couple breast tumor size and metastatic spread
journal, April 2007
- Minn, A. J.; Gupta, G. P.; Padua, D.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 16
Weighing of biomolecules, single cells and single nanoparticles in fluid
journal, April 2007
- Burg, Thomas P.; Godin, Michel; Knudsen, Scott M.
- Nature, Vol. 446, Issue 7139
Performance Analysis of the Lattice Boltzmann Model Beyond Navier-Stokes
conference, May 2013
- Randles, Amanda Peters; Kale, Vivek; Hammond, Jeff
- 2013 IEEE International Symposium on Parallel & Distributed Processing (IPDPS), 2013 IEEE 27th International Symposium on Parallel and Distributed Processing