The Impact of Mechanical Cues on the Metabolomic and Transcriptomic Profiles of Human Dermal Fibroblasts Cultured in Ultrashort Self-Assembling Peptide 3D Scaffolds

Sherin Abdelrahman, Rui Ge, Hepi H. Susapto, Yang Liu, Faris Samkari, Manola Moretti, Xinzhi Liu, Robert Hoehndorf, Abdul Hamid Emwas, Mariusz Jaremko, Ranim H. Rawas, Charlotte A.E. Hauser*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Cells’ interactions with their microenvironment influence their morphological features and regulate crucial cellular functions including proliferation, differentiation, metabolism, and gene expression. Most biological data available are based on in vitro two-dimensional (2D) cellular models, which fail to recapitulate the three-dimensional (3D) in vivo systems. This can be attributed to the lack of cell-matrix interaction and the limitless access to nutrients and oxygen, in contrast to in vivo systems. Despite the emergence of a plethora of 3D matrices to address this challenge, there are few reports offering a proper characterization of these matrices or studying how the cell-matrix interaction influences cellular metabolism in correlation with gene expression. In this study, two tetrameric ultrashort self-assembling peptide sequences, FFIK and FIIK, were used to create in vitro 3D models using well-described human dermal fibroblast cells. The peptide sequences are derived from naturally occurring amino acids that are capable of self-assembling into stable hydrogels without UV or chemical cross-linking. Our results showed that 2D cultured fibroblasts exhibited distinct metabolic and transcriptomic profiles compared to 3D cultured cells. The observed changes in the metabolomic and transcriptomic profiles were closely interconnected and influenced several important metabolic pathways including the TCA cycle, glycolysis, MAPK signaling cascades, and hemostasis. Data provided here may lead to clearer insights into the influence of the surrounding microenvironment on human dermal fibroblast metabolic patterns and molecular mechanisms, underscoring the importance of utilizing efficient 3D in vitro models to study such complex mechanisms.

Original languageEnglish (US)
Pages (from-to)14508-14531
Number of pages24
JournalACS Nano
Volume17
Issue number15
DOIs
StatePublished - Aug 8 2023

Bibliographical note

Publisher Copyright:
© 2023 American Chemical Society.

Keywords

  • 3D culturing
  • 3D in vitro tissue models
  • human dermal fibroblasts
  • metabolomics
  • natural and synthetic matrices
  • transcriptomics
  • ultrashort self-assembling peptides

ASJC Scopus subject areas

  • General Materials Science
  • General Engineering
  • General Physics and Astronomy

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