Ligand Binding-Induced Cellular Membrane Deformation is Correlated with the Changes in Membrane Stiffness.
Jayeeta KolayPengfei ZhangXinyu ZhouZijian WanAndy ChiengShaopeng WangPublished in: The journal of physical chemistry. B (2023)
Study interaction between ligands and protein receptors is a key step for biomarker research and drug discovery. In situ measurement of cell surface membrane protein binding on whole cells eliminates the cost and pitfalls associated with membrane protein purification. Ligand binding to membrane protein was recently found to induce nanometer-scale cell membrane deformations, which can be monitored with real-time optical imaging to quantify ligand/protein binding kinetics. However, the insight into this phenomenon has still not been fully understood. We hypothesize that ligand binding can change membrane stiffness, which induces membrane deformation. To investigate this, cell height and membrane stiffness changes upon ligand binding are measured using atomic force microscopy (AFM). Wheat germ agglutinin (WGA) is used as a model ligand that binds to the cell surface glycoprotein. The changes in cell membrane stiffness and cell height upon ligand bindings are determined for three different cell lines (human A431, HeLa, and rat RBL-2H3) on two different substrates. AFM results show that cells become stiffer with increased height after WGA modification for all cases studied. The increase in cell membrane stiffness is further confirmed by plasmonic scattering microscopy, which shows an increased cell spring constant upon WGA binding. Therefore, this study provides direct experimental evidence that the membrane stiffness changes are directly correlated with ligand binding-induced cell membrane deformation.
Keyphrases
- atomic force microscopy
- cell surface
- high speed
- single cell
- body mass index
- induced apoptosis
- single molecule
- high resolution
- cell cycle arrest
- drug discovery
- cell therapy
- dna binding
- cell death
- mass spectrometry
- drug induced
- transcription factor
- protein protein
- bone marrow
- signaling pathway
- optical coherence tomography
- pi k akt
- quantum dots