Closer to Nature Through Dynamic Culture Systems

Abstract

Mechanics in the human body are required for normal cell function at a molecular level. It is now clear that mechanical stimulations play significant roles in cell growth, differentiation, and migration in normal and diseased cells. Recent studies have led to the discovery that normal and cancer cells have different mechanosensing properties. Here, we discuss the application and the physiological and pathological meaning of mechanical stimulations. To reveal the optimal conditions for mimicking an in vivo microenvironment, we must, therefore, discern the mechanotransduction occurring in cells.

Keywords: mechanical stimulation; mechanosensing; mechanotransduction.

Figure 1

An illustration that depicts the concept of understanding the human dynamic system through mechanical stimulations of human cells. In this concept, all dynamics are bio-inspired by the living entity itself through motions, such as running, balancing, bouncing, and compressing. Mechanical stimuli applied to the in vitro system better mimic mechanical cues in nature, such as a strain of muscle in motion. Therefore, this concept conveys the idea of finding organ or tissue substitutes in the future. D: dimension; MS: mechanical stimulation.

Figure 2

An illustration showing the effect of mechanical stimulation on different cells. (A) In vivo, mechanical stimulations activate specific ion channels, such as Piezo1, and Piezo2, in various types of cells: muscle, non-muscle, progenitor, and diseased cells. The surrounding extracellular matrix (ECM) interacts with the cells to regulate intracellular intermediate filament rearrangement, which in turn modulates the cell nucleus morphology. Upon sensing the signal, nuclear cytoskeletal proteins realign to regulate gene transcription. (B) Blood pressure exerts mechanical force on endothelial cells, which express Piezo1 to sense the exerted force. (C) When the joints are compressed, bone cells experience a compressive force that is sensed by type 1 parathyroid hormone receptor (PTH1R) on bone lining cells, which regulates growth and differentiation of osteocytes. (D) Evidence shows that mechanical force improves the maturation of cardiomyocytes differentiated from induced pluripotent stem cells (iPSCs), so that they show a similar structure as cardiac tissue and can be transplanted into an animal’s heart.