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Hydrogels designed for preventing bacterial adhesion based on the response mechanism of Staphylococcus aureus to material stiffness

Leyi Xiao,Chen Chen,Mengge Feng,Yulan Wang,Tiange Zhang,Yueqi Ni,Fanyu Zhang,Jiaojiao Li,Qi Xiao,Yu Cui,Yufeng Zhang

Medical implants have opened up more possibilities in clinical medicine, while they may lead to severe complications due to biofilm formed by bacteria. Understanding the bacterial response mechanism to the material's stiffness is critical to preventing biofilm formation. This study used Staphylococcus aureus , one of the most common clinical pathogens, to explore the response mechanism. Based on the results, bacteria adhere more efficiently with lower membrane potential on stiff hydrogels than soft hydrogels. Combining experiments and molecular dynamics simulations, we found that the Arsenical pump membrane protein (ArsB) of S. aureus was upregulated on stiff hydrogels and can modulate the bacterial membrane potential and adhesion. The interface membrane curvature was the main morphology difference between bacteria on soft and stiff hydrogels. With the more significant membrane deformation of the bacteria on stiff hydrogels, we demonstrated that the changes in membrane curvature could open the ArsB ion channel. Finally, we screened the ArsB inhibitory drug Rapamycin and verified that Rapamycin-loaded hydrogels could efficiently prevent bacterial adhesion. It can be a way of inhibiting bacterial adhesion during biofilm formation and provide directions for the design of future medical materials.