Using polyrotaxane as a biointerface may become a powerful tool to improve the physical immune system and repair biological tissues.
In the field of tissue engineering, scientists are constantly testing the possibility of harnessing the different properties of various biomaterials to achieve tissue regeneration. A key factor in creating effective tissues that can improve upon and act as physical barriers is the strength of cell-cell adhesion. Now, scientists at Tokyo Medical and Dental University have demonstrated that culturing epithelial cells on a biomaterial surface using polyrotaxane can improve cell-cell adhesion to repair damaged tissues for regeneration.
Polyrotaxanes are a specialised class of supramolecular assemblies that consist of strings and rings in which multiple ring-like molecules are threaded onto a molecular axle and prevented from dethreading by two bulky end groups. They can display molecular mobility like the sliding or rotation of ring-shaped molecules along an axle molecule. When cells are cultured on this biomaterial, the molecular mobility of polyrotaxanes can influence cell-cell adhesion through one of its main players, a protein called yes-associated protein (YAP).
“We knew that cell-cell adhesion is closely related to the subcellular localisation of YAP,” says Ryo Mikami, one of the lead authors of the study. “For instance, increasing cytoplasmic YAP localisation promotes the organisation of tight junctions, which are specialised connections between two adjacent cells. Therefore, we hypothesised that cell-cell adhesion of epithelial cells could be enhanced by YAP being affected through the molecular mobility of polyrotaxane surfaces.”
Using cells derived from mouse lung as a model of epithelial cells, the researchers cultured the cells on the polyrotaxane surfaces with different mobility and studied their proliferation and morphology. The team then used fluorescent staining to visualise the subcellular localisation of YAP to determine whether it was in the cytoplasm or in the nucleus.
Their analyses showed that polyrotaxane surfaces with high mobility caused the cytoplasmic localisation of YAP, which increased the expression of tight junction-associated genes and thereby caused stronger cell-cell adhesion. In contrast, those with low mobility resulted in nuclear YAP localisation. Furthermore, a scratch assay revealed that the epithelial cells on the low mobile surface rapidly migrated. In contrast, the cells on the highly mobile surface delayed their migration. These results demonstrate the potential of polyrotaxane biointerface as a powerful tool to improve the physical immune system and repair biological tissues.
“In the future, polyrotaxane-based biomaterials with tuned molecular mobility represent promising implantable biomaterials for reinforcing the physical barrier function of epithelial tissues and inhibiting the progression of inflammation,” commented Nobuhiko Yui, senior author on the study.
Additionally, polyrotaxane surfaces could be applied in clinical dentistry to help treat periodontal disease, where damage to tight junctions due to bacterial infections is known to cause gingivitis and periodontitis. Such biomaterials that boost cell-cell adhesion are expected to not only support tissue reconstruction but also to help heal and repair damaged tissues by reducing inflammation and restoring the physical barrier to protect against microorganisms. [APBN]
Source: Mikami et al. (2021). Improved epithelial cell–cell adhesion using molecular mobility of supramolecular surfaces. Biomaterials Science, 9(21), 7151–7158.