Abstract
Vascular endothelial cells form a barrier that blocks the delivery of drugs entering into brain tissue for central nervous system disease treatment. The mechanical responses of vascular endothelial cells play a key role in the progress of drugs passing through the blood–brain barrier. Although nanoindentation experiment by using AFM (Atomic Force Microscopy) has been widely used to investigate the mechanical properties of cells, the particular mechanism that determines the mechanical response of vascular endothelial cells is still poorly understood. In order to overcome this limitation, nanoindentation experiments were performed at different loading rates during the ramp stage to investigate the loading rate effect on the characterization of the mechanical properties of bEnd.3 cells (mouse brain endothelial cell line). Inverse finite element analysis was implemented to determine the mechanical properties of bEnd.3 cells. The loading rate effect appears to be more significant in short-term peak force than that in long-term force. A higher loading rate results in a larger value of elastic modulus of bEnd.3 cells, while some mechanical parameters show ambiguous regulation to the variation of indentation rate. This study provides new insights into the mechanical responses of vascular endothelial cells, which is important for a deeper understanding of the cell mechanobiological mechanism in the blood–brain barrier.
Highlights
The incidence of central nervous system (CNS) diseases represents a prevalent and heavy burden on the global health community, despite a significant improvement in the understanding of the pathological mechanisms [1]
Changes in the mechanical properties of Vascular endothelial cells (VECs) accompany a variation in the blood–brain barrier, which is due to these cells being the main barriers to the flow of ions, nutrients, and other nanoparticles meeting during the entering process into the brain tissue [7,8]
The current study presents a novel approach that combined AFM experiment with finite element simulation and optimization algorithms to obtain the mechanical properties of a single bEnd.3 cell
Summary
The incidence of central nervous system (CNS) diseases represents a prevalent and heavy burden on the global health community, despite a significant improvement in the understanding of the pathological mechanisms [1]. The blood–brain barrier represents a unique interface that regulates the flowing of ions, nutrients, and other compounds entering into the brain tissue [4]. It is a double-edged sword in that the BBB plays a vital role in maintaining homeostasis and protecting the brain from pathogens invasion, the BBB blocks the transportation of drugs for the treatment of CNS diseases. Vascular endothelial cells (VECs) exist around the blood vessel and comprise the interface between blood and the surrounding tissue [5] These cells form the basis of the blood–brain- barrier, and the characterization of these cells is key to understanding pathologies and treating central nervous system disorders [6]. Proper and accurate quantification of the mechanical properties of vascular endothelial cells is a key step to further understand the mechanism of blood–brain barrier, which has not been comprehensively understood until now
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