Hybrid cellular Potts and bead-spring modeling of cells in fibrous extracellular matrix

Tsingos, Erika; Bakker, Bente Hilde; Keijzer, Koen A.E.; Hupkes, Hermen Jan; Merks, Roeland

doi:10.1016/j.bpj.2023.05.013

Cited by 11 publications

(15 citation statements)

References 133 publications

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“…The discrete-to-continuum modelling approach is not restricted to cytoskeletal networks and could similarly be applied to other cross-linked networks of semi-flexible filaments such as collagen [44]. Furthermore, our approach could be modified to model cells migrating through (and interacting with) extracellular matrix [25,63,64].…”

Section: Discussionmentioning

confidence: 99%

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Discrete-to-continuum models of pre-stressed cytoskeletal filament networks

Köry,

Hill,

Luo

et al. 2024

Proc. R. Soc. A.

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We introduce a mathematical model for the mechanical behaviour of the eukaryotic cell cytoskeleton. This discrete model involves a regular array of pre-stressed protein filaments that exhibit resistance to enthalpic stretching, joined at cross-links to form a network. Assuming that the inter-cross-link distance is much shorter than the length scale of the cell, we upscale the discrete force balance to form a continuum system of governing equations and deduce the corresponding macroscopic stress tensor. We use these discrete and continuum models to analyse the imposed displacement of a bead placed in the domain, characterizing the cell rheology through the force–displacement curve. We further derive an analytical approximation to the stress and strain fields in the limit of small bead radius, predicting the net force required to generate a given deformation and elucidating the dependency on the microscale properties of the filaments. We apply these models to networks of the intermediate filament vimentin and demonstrate good agreement between predictions of the discrete, continuum and analytical approaches. In particular, our model predicts that the network stiffness increases sublinearly with the filament pre-stress and scales logarithmically with the bead size.

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Section: Discussionmentioning

confidence: 99%

“…such as collagen [44]. Furthermore, our approach could be modified to model cells migrating through (and interacting with) extracellular matrix [25,63,64].…”

Section: Appendix a Application To Disordered Filament Networkmentioning

confidence: 99%

Discrete-to-continuum models of pre-stressed cytoskeletal filament networks

Köry,

Hill,

Luo

et al. 2024

Proc. R. Soc. A.

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“…We introduced a linear elastic fiber network simulation to model the feedback of cellular traction forces within a fibrous morphological environment . This arrangement highlighted that the fiber-like matrix exhibited stiffening under strain.…”

Section: Hydrogels With Aligned and Random Topographiesmentioning

confidence: 99%

“…We introduced a linear elastic fiber network simulation to model the feedback of cellular traction forces within a fibrous morphological environment. 29 This arrangement highlighted that the fiber-like matrix exhibited stiffening under strain. During the simulation, a horizontal force was applied to the right at random points along the fibers with varying orientations.…”

mentioning

confidence: 93%

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Synergistic Influence of Fibrous Pattern Orientation and Modulus on Cellular Mechanoresponse

Sun,

Pan,

Wang

et al. 2024

Nano Lett.

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The fibrous extracellular matrix (ECM) is vital for tissue regeneration and impacts implanted device treatments. Previous research on fibrous biomaterials shows varying cellular reactions to surface orientation, often due to unclear interactions between surface topography and substrate elasticity. Our study addresses this gap by achieving the rapid creation of hydrogels with diverse fibrous topographies and varying substrate moduli through a surface printing strategy. Cells exhibit heightened traction force on nanopatterned soft hydrogels, particularly with randomly distributed patterns compared with regular soft hydrogels. Meanwhile, on stiff hydrogels featuring an aligned topography, optimal cellular mechanosensing is observed compared to random topography. Mechanistic investigations highlight that cellular force-sensing and adhesion are influenced by the interplay of pattern deformability and focal adhesion orientation, subsequently mediating stem cell differentiation. Our findings highlight the importance of combining substrate modulus and topography to guide cellular behavior in designing advanced tissue engineering biomaterials.

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