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Multimodal Characterization of the Collagen Hydrogel Structure and Properties in Response to Physiologically Relevant Ph Fluctuations

25 Pages Posted: 20 Sep 2023 Publication Status: Published

See all articles by Orit Shtrauchler

Orit Shtrauchler

Ben-Gurion University of the Negev

Einat Nativ-Roth

Ben-Gurion University of the Negev

Daniel Sevilla Sanchez

Ben-Gurion University of the Negev

Michal Zaiden

Ben-Gurion University of the Negev

Netta Vidavsky

Ben-Gurion University of the Negev - Department of Chemical Engineering

Abstract

pH fluctuations within the extracellular matrix (ECM) and its principal constituent collagen, particularly in solid tumors and chronic wounds, may influence its structure and function. Whereas previous research examined the impact of pH on collagen fibrillogenesis, this study focuses on determining how pH fluctuations affect collagen hydrogels that mimic the physiological ECM. Utilizing a type I collagen hydrogel, we examined the influence of pH fluctuations on its structure, properties, and function while keeping the collagen hydrated. We show that collagen's secondary structure remains unaltered during pathologically relevant microenvironmental pH changes. By employing cryo Scanning Electron Microscopy and Artificial Intelligence-assisted image analysis, we show that at physiological pH, collagen hydrogel presents densely packed, aligned, and elongated fibrils, which upon a decrease to pH 6.5, are transformed into shorter, sparser, and disoriented fibrils. The collagen possesses a higher storage modulus yet a lower permeability at pH 7 and 7.8 compared with pH 6.5 and 7.4. Exposing acidified collagen to a basic buffer reinstates its native structure and viscoelastic properties. Our study offers an innovative approach to analyze and characterize perturbations in hydrated collagen-based systems with potential implications for better understanding and combating disease progression.

Keywords: tumor microenvironment, Cryo Scanning Electron Microscopy, extracellular matrix

Suggested Citation

Shtrauchler, Orit and Nativ-Roth, Einat and Sevilla Sanchez, Daniel and Zaiden, Michal and Vidavsky, Netta, Multimodal Characterization of the Collagen Hydrogel Structure and Properties in Response to Physiologically Relevant Ph Fluctuations. Available at SSRN: https://ssrn.com/abstract=4574978 or http://dx.doi.org/10.2139/ssrn.4574978

Orit Shtrauchler

Ben-Gurion University of the Negev ( email )

1 Ben-Gurion Blvd
Beer-Sheba 84105, 84105
Israel

Einat Nativ-Roth

Ben-Gurion University of the Negev ( email )

1 Ben-Gurion Blvd
Beer-Sheba 84105, 84105
Israel

Daniel Sevilla Sanchez

Ben-Gurion University of the Negev ( email )

1 Ben-Gurion Blvd
Beer-Sheba 84105, 84105
Israel

Michal Zaiden

Ben-Gurion University of the Negev ( email )

1 Ben-Gurion Blvd
Beer-Sheba 84105, 84105
Israel

Netta Vidavsky (Contact Author)

Ben-Gurion University of the Negev - Department of Chemical Engineering ( email )

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