Elastic Cytomatrix Dynamics Influences Metabolic Rate and Tumor Microenvironment Formation

TL;DR

This paper explores how the elastic structure inside cells, called the cytomatrix, influences metabolism and tumor formation by interacting with the surrounding environment.

Contribution

The paper introduces a novel perspective on cytomatrix dynamics and their role in tumor microenvironment formation through altered protein translocation and immune interactions.

Findings

Cytomatrix dynamics regulate metabolism and are more intense in cancer cells.

ECM proteins translocate to the cell surface, influencing immune responses and tumor niche formation.

Altered cytomatrix mechanics contribute to cancer cell dedifferentiation and immune evasion.

Abstract

Traditionally, the chemical reactions that occur within cells are viewed as processes in an aqueous solution with free diffusion. However, the cytoplasm is organized as a two-phase system consisting of a viscous fluid, the cytosol, and an elastic solid matrix, the cytomatrix. The solid phase contains immobilized enzymes that operate without spatial constraints, enabling chemical processes to occur simultaneously without interference. The dynamics of the cytomatrix regulate the rate of metabolism through cytosolic movement, manifesting as cytoplasmic fluctuations that are more intense in cancer cells. The intracellular cytomatrix interacts with the extracellular matrix (ECM). The ECM proteoglycans and glycoproteins produced by the cytomatrix serve as markers for tissue cells and are crucial for cell recognition, signaling, and immune surveillance and response. Translocation of mutated ECM proteins to the cell surface may trigger an immune response, attract various stromal cells, and form a tumor microenvironment.

In healthy cells, the cytomatrix mechanics utilize mitochondrial respiration to control cytosolic motion and fine-tune the chemical processes. In cancer, the cytosolic motion is energized by glycolytic fermentation (the Warburg effect), which provides additional energy to supply the needs of the cytomatrix. Here, we describe the physical and chemical processes of the integrated and cooperative cytomatrix cytoarchitecture, in which structure and function are inseparable. The extracellular matrix is interconnected with the intracellular cytomatrix and functions as two integrated elastic solid phases. This finding led us to propose mechanisms of tumor microenvironment formation resulting from the mutational burden, in which altered proteins with corresponding post-translational modifications translocate to the cell surface, where they attract immunocompetent cells and activated fibroblasts, producing a tumor-insulating niche. This insulation disrupts cell-to-cell recognition and other signaling pathways that affect the intracellular cytomatrix, particularly actin dynamics, which influence both cell size and shape, recognized as the dedifferentiated state of cancer cells. We also discuss the perspectives of AI in cytomatrix modeling and neural network modeling, focusing on the effects of intracellular and extracellular matrices on the development of the tumor microenvironment.

Figures