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Cells
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Multiscale Studies of Cell Behavior
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Multiscale Studies of Cell Behavior

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (15 July 2023) | Viewed by 3411

Special Issue Editor

Dr. Denis Tsygankov

E-Mail Website
Guest Editor
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta, GA 30332, USA
Interests: cell biomechanics; systems biology; multiscale modeling and simulations; vasculogenesis; metastasis

Special Issue Information

Dear Colleagues,

A mechanistic understanding of physiological processes is impossible without bridging our knowledge across multiple spatiotemporal scales, from gene regulation to organ function. Even at the level of cell function, we face the challenge of connecting molecular interactions to the formation of macromolecular structures and their coordinated dynamics driving cell motion, division, and interaction with other cells and the extracellular environment. For decades, researchers have focused on isolated scales extracting essential information about the mechanism operating at those scales. However, continuous progress in experimental technologies and computational methodologies opens new opportunities for a more comprehensive, systems-level view of cell behavior. Such opportunities, in turn, stimulate study designs that rely on a close integration of multidisciplinary approaches.

This Special Issue aims to bring together researchers from different subfields of cell biology using or developing computational and experimental methods to study various cellular processes from the multiscale perspective. The processes of interest include, but are not limited to, collective cell behavior, motility, biomechanics, and dynamic coordination of regulatory and structural elements across the cell or cell aggregates in any biological or biomedical context.

Dr. Denis Tsygankov
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • multiscale
  • systems level
  • coordinated regulation
  • motility
  • biomechanics
  • imaging
  • optogenetics
  • computational methods
  • simulation
  • complex dynamics

Published Papers (2 papers)

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Research

26 pages, 4294 KiB  
Article
Breast Cancer Cell Type and Biomechanical Properties of Decellularized Mouse Organs Drives Tumor Cell Colonization
by Anton D. Pospelov, Olga M. Kutova, Yuri M. Efremov, Albina A. Nekrasova, Daria B. Trushina, Sofia D. Gefter, Elena I. Cherkasova, Lidia B. Timofeeva, Peter S. Timashev, Andrei V. Zvyagin and Irina V. Balalaeva
Cells 2023, 12(16), 2030; https://doi.org/10.3390/cells12162030 - 9 Aug 2023
Cited by 1 | Viewed by 1789
Abstract
Tissue engineering has emerged as an indispensable tool for the reconstruction of organ-specific environments. Organ-derived extracellular matrices (ECM) and, especially, decellularized tissues (DCL) are recognized as the most successful biomaterials in regenerative medicine, as DCL preserves the most essential organ-specific ECM properties such [...] Read more.
Tissue engineering has emerged as an indispensable tool for the reconstruction of organ-specific environments. Organ-derived extracellular matrices (ECM) and, especially, decellularized tissues (DCL) are recognized as the most successful biomaterials in regenerative medicine, as DCL preserves the most essential organ-specific ECM properties such as composition alongside biomechanics characterized by stiffness and porosity. Expansion of the DCL technology to cancer biology research, drug development, and nanomedicine is pending refinement of the existing DCL protocols whose reproducibility remains sub-optimal varying from organ to organ. We introduce a facile decellularization protocol universally applicable to murine organs, including liver, lungs, spleen, kidneys, and ovaries, with demonstrated robustness, reproducibility, high purification from cell debris, and architecture preservation, as confirmed by the histological and SEM analysis. The biomechanical properties of as-produced DCL organs expressed in terms of the local and total stiffness were measured using our facile methodology and were found well preserved in comparison with the intact organs. To demonstrate the utility of the developed DCL model to cancer research, we engineered three-dimensional tissue constructs by recellularization representative decellularized organs and collagenous hydrogel with human breast cancer cells of pronounced mesenchymal (MDA-MB-231) or epithelial (SKBR-3) phenotypes. The biomechanical properties of the DCL organs were found pivotal to determining the cancer cell fate and progression. Our histological and scanning electron microscopy (SEM) study revealed that the larger the ECM mean pore size and the smaller the total stiffness (as in lung and ovary), the more proliferative and invasive the mesenchymal cells became. At the same time, the low local stiffness ECMs (ranged 2.8–3.6 kPa) did support the epithelial-like SKBR-3 cells’ viability (as in lung and spleen), while stiff ECMs did not. The total and local stiffness of the collagenous hydrogel was measured too low to sustain the proliferative potential of both cell lines. The observed cell proliferation patterns were easily interpretable in terms of the ECM biomechanical properties, such as binding sites, embedment facilities, and migration space. As such, our three-dimensional tissue engineering model is scalable and adaptable for pharmacological testing and cancer biology research of metastatic and primary tumors, including early metastatic colonization in native organ-specific ECM. Full article
(This article belongs to the Special Issue Multiscale Studies of Cell Behavior)
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28 pages, 7918 KiB  
Article
Spatiotemporal Coordination of Rac1 and Cdc42 at the Whole Cell Level during Cell Ruffling
by Siarhei Hladyshau, Jorik P. Stoop, Kosei Kamada, Shuyi Nie and Denis Tsygankov
Cells 2023, 12(12), 1638; https://doi.org/10.3390/cells12121638 - 15 Jun 2023
Viewed by 1257
Abstract
Rho-GTPases are central regulators within a complex signaling network that controls cytoskeletal organization and cell movement. The network includes multiple GTPases, such as the most studied Rac1, Cdc42, and RhoA, along with their numerous effectors that provide mutual regulation through feedback loops. Here [...] Read more.
Rho-GTPases are central regulators within a complex signaling network that controls cytoskeletal organization and cell movement. The network includes multiple GTPases, such as the most studied Rac1, Cdc42, and RhoA, along with their numerous effectors that provide mutual regulation through feedback loops. Here we investigate the temporal and spatial relationship between Rac1 and Cdc42 during membrane ruffling, using a simulation model that couples GTPase signaling with cell morphodynamics and captures the GTPase behavior observed with FRET-based biosensors. We show that membrane velocity is regulated by the kinetic rate of GTPase activation rather than the concentration of active GTPase. Our model captures both uniform and polarized ruffling. We also show that cell-type specific time delays between Rac1 and Cdc42 activation can be reproduced with a single signaling motif, in which the delay is controlled by feedback from Cdc42 to Rac1. The resolution of our simulation output matches those of time-lapsed recordings of cell dynamics and GTPase activity. Our data-driven modeling approach allows us to validate simulation results with quantitative precision using the same pipeline for the analysis of simulated and experimental data. Full article
(This article belongs to the Special Issue Multiscale Studies of Cell Behavior)
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