The mechanism by which Fmoc-Arg(Pbf)-OH promotes cell adhesion and proliferation mainly involves the following aspects:
I. Interaction with Cell Surface Receptors
The arginine (Arg) residue in Fmoc-Arg(Pbf)-OH is a key structure. There are various receptors on the cell surface, such as the integrin family. Integrins can recognize and bind to specific amino acid sequences in the extracellular matrix. The arginine-glycine-aspartic acid (RGD) sequence is a classic recognition site for integrins. Although it is not a typical RGD sequence, the arginine residue has similarities in spatial structure and chemical properties to the arginine in the RGD sequence. After Fmoc-Arg(Pbf)-OH is modified on the surface of the tissue engineering scaffold, the arginine residue can specifically bind to the integrin receptor, thereby mediating the adhesion between the cell and the scaffold surface. This binding will activate the intracellular signaling pathway, such as the focal adhesion kinase (FAK) signaling pathway, and then promote the reorganization of the cytoskeleton and the formation of focal adhesions, enabling the cells to adhere firmly to the scaffold surface.
II. Regulation of the Assembly of the Extracellular Matrix
The extracellular matrix (ECM) plays an important role in cell adhesion, proliferation, and differentiation. Fmoc-Arg(Pbf)-OH can affect the secretion and assembly of ECM components. On the one hand, it can activate the intracellular signaling pathway through interaction with cell surface receptors, promoting the secretion of ECM-related proteins by cells, such as collagen and fibronectin. On the other hand, it can also serve as a template or scaffold to guide the deposition and assembly of ECM proteins, forming a microenvironment conducive to cell adhesion and proliferation. For example, Fmoc-Arg(Pbf)-OH can interact with collagen, promoting the cross-linking of collagen molecules and the formation of fibers, thereby enhancing the stability and functionality of the ECM, providing more adhesion sites for cells and better mechanical support, and further promoting cell adhesion and proliferation.
III. Influence on Intracellular Signaling Pathways
After Fmoc-Arg(Pbf)-OH binds to cell surface receptors, in addition to activating the FAK signaling pathway, it can also trigger a series of other signaling events. For example, it can activate the PI3K-AKT signaling pathway, which plays a key role in processes such as cell survival, proliferation, and metabolism. After AKT is activated, it will phosphorylate a variety of downstream target proteins, such as the mammalian target of rapamycin (mTOR), thereby promoting protein synthesis and the cell cycle process, and driving the cells from the quiescent phase into the proliferative phase. In addition, Fmoc-Arg(Pbf)-OH may also affect the mitogen-activated protein kinase (MAPK) signaling pathway, such as activating extracellular signal-regulated kinase (ERK). After ERK enters the nucleus, it can regulate the expression of genes related to cell proliferation and promote cell division and proliferation.
IV. Improvement of the Physicochemical Properties of the Scaffold Surface
After Fmoc-Arg(Pbf)-OH is modified on the surface of the tissue engineering scaffold, it will change the physicochemical properties of the scaffold surface. The arginine residue is positively charged, changing the charge distribution on the scaffold surface, which is beneficial for negatively charged cells to be attracted to the scaffold surface, increasing the contact opportunities between cells and the scaffold. At the same time, the presence of Fmoc-Arg(Pbf)-OH can also regulate the hydrophilicity and hydrophobicity of the scaffold surface. The Fmoc group has a certain degree of hydrophobicity, while the arginine residue is hydrophilic. This amphiphilic structure can form an appropriate hydrophilic-hydrophobic balance on the scaffold surface, which is beneficial for cell adhesion and can ensure that the microenvironment around the cells has good material exchange capabilities, providing necessary nutrients and growth factors for cells, thus promoting cell adhesion and proliferation.
