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Tension in the ranks: Cooperative cell contractions drive force-dependent collagen assembly in human fibroblast culture.

Alexandra A Silverman | Jason D Olszewski | Seyed Mohammad Siadat | Jeffrey W Ruberti
Matter | 2024

Currently, there is no mechanistic model that fully explains the initial synthesis and organization of durable animal structure. As a result, our understanding of extracellular matrix (ECM) development and pathologies (e.g., persistent fibrosis) remains limited. Here, we identify and characterize cell-generated mechanical strains that direct the assembly of the ECM. Cell kinematics comprise cooperative retrograde "pulls" that organize and precipitate biopolymer structure along lines of tension. High-resolution optical microscopy revealed five unique classes of retrograde "pulls" that result in the production of filaments. Live-cell confocal imaging confirmed that retrograde pulls can directly cause the formation of fibronectin filaments that then colocalize with collagen aggregates exported from the cell, producing persistent elongated structures aligned with the direction of the tension. The findings suggest a new model for initial durable structure formation in animals. The results have important implications for ECM development and growth and life-threatening pathologies of the ECM, such as fibrosis.

Pubmed ID: 40213036

Associated grants

  • Agency: NEI NIH HHS, United States
    Id: R01 EY034124
  • Agency: NEI NIH HHS, United States
    Id: R21 EY029167

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ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

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Fiji (tool)

RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

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Sigma-Aldrich (tool)

RRID:SCR_008988

American chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.

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Abcam (tool)

RRID:SCR_012931

A commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.

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Northeastern University Institute for Chemical Imaging of Living Systems Core Facility (service resource)

RRID:SCR_022681

Located in ISEC research center and includes advanced imaging instruments. CILS has three core facilities: Microscopy Core (confocal/multi-photon/lightsheet microscopes), Flow Cytometry Core (cell analyzer/sorter) and Preclinical Imaging Core (3T small animal MRI and ultrasound).

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