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

by S. Abdelrahman, R. Ge, H.H. Susapto, Y. Liu, F. Samkari, M. Moretti, X. Liu, R. Hoehndorf, A.-H. Emwas, M. Jaremko, R. H. Rawas, C.A.E. Hauser
Year:2023 DOI:


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.


scaffolds ultrashort self-assembling peptides Biophysical cues Metabolomics Transcriptomics

"KAUST shall be a beacon for peace, hope and reconciliation, and shall serve the people of the Kingdom and the world."

King Abdullah bin Abdulaziz Al Saud, 1924 – 2015

Contact Us

  • 4700 King Abdullah University of Science and Technology

    Thuwal 23955-6900, Kingdom of Saudi Arabia

    Al-Haytham Building (Bldg. 2)

Quick links

© King Abdullah University of Science and Technology. All rights reserved