What Are the Effects of MβCD on the Cytoskeleton and Cell Mechanics?
Methyl-β-cyclodextrin (MβCD) is a methylated derivative of the cyclic oligosaccharide β-cyclodextrin, which itself consists of seven α-(1→4)-linked glucopyranose rings. The hydroxyl groups (mainly on the C2 position) of methyl-β-cyclodextrin are chemically modified with methyl groups. The derivatization of the native β-cyclodextrin results in an amphiphilic molecule with a hydrophilic exterior and a hydrophobic cavity interior. The molecule's dual affinity characteristics allow it to encapsulate nonpolar or hydrophobic compounds, enhancing their solubility, stability, and bioavailability in aqueous environments.
Methyl-β-cyclodextrin (MβCD) profoundly influences cell mechanics through its ability to depolymerize actin filaments without disturbing microtubules. This selective disassembly impairs the formation of focal adhesions—cellular anchor points regulated by proteins such as paxillin and phosphorylated FAK (pFAK). Immunostaining studies revealed that MβCD reduced paxillin and pFAK focal adhesion areas by 56% and 66%, respectively, in HeLa cells. Furthermore, atomic force microscopy demonstrated a 50% reduction in cell stiffness post-treatment, while traction force microscopy showed a 65% drop in cellular traction force.
Such biomechanical alterations also affect cell deadhesion kinetics. MβCD-treated cells exhibited significantly shortened τ1 values (initial detachment) and modestly prolonged τ2 values (subsequent detachment), indicating altered adhesion strength and cytoskeletal dynamics. These findings underscore MβCD's potential utility in mechanobiology research and drug delivery optimization.
Created: 17 Jul 2025 02:07:01 AM
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