Mechanical Studies of the Third Dimension in Cancer: From 2D to 3D Model

Abstract

From the development of self-aggregating, scaffold-free multicellular spheroids to the inclusion of scaffold systems, 3D models have progressively increased in complexity to better mimic native tissues. The inclusion of a third dimension in cancer models allows researchers to zoom out from a significant but limited cancer cell research approach to a wider investigation of the tumor microenvironment. This model can include multiple cell types and many elements from the extracellular matrix (ECM), which provides mechanical support for the tissue, mediates cell-microenvironment interactions, and plays a key role in cancer cell invasion. Both biochemical and biophysical signals from the extracellular space strongly influence cell fate, the epigenetic landscape, and gene expression. Specifically, a detailed mechanistic understanding of tumor cell-ECM interactions, especially during cancer invasion, is lacking. In this review, we focus on the latest achievements in the study of ECM biomechanics and mechanosensing in cancer on 3D scaffold-based and scaffold-free models, focusing on each platform's level of complexity, up-to-date mechanical tests performed, limitations, and potential for further improvements.

Keywords: 3D model; biomaterials; cancer; mechanics; mechanosensing; microenvironment.

Figure 1

Mechanical coupling of the extracellular matrix with the nucleus: Mechanical signal propagation through molecular pathways inside the cytosol and nucleus. Made with Biorender.

Figure 2

Classification of the most common cancer study models with their strengths and limitations. The primary mechanical tests performed on each platform are reported in italics. Biological and technical characteristics of the cancer model are highlighted. On the bottom, 3D in vitro systems cellular complexity and accessibility of imaging and analysis. Made with Biorender.