همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Fluidity of normal and cancer cell membranes: A molecular dynamics investigation

نویسندگان :

Elahe Hoseinnia¹ Mahboobeh Zarrabi²

1- Alzahra University 2- Alzahra University

کلمات کلیدی :

Molecular Dynamics Simulation،Biomembrane،Cancer،Fluidity

چکیده :

Plasma membranes are necessary for physiological functions and regulate intracellular signaling, redox balance and cell death (Preta, 2020). The membrane consists of lipids and proteins(Szlasa et al., 2020). Chemical or functional changes in membranes are central to the pathogenesis of the disease (Goldberg and Riordan, 1986). Cancer is one of these diseases. Cancerous cells show alterations in their membrane’s lipid profile and biophysical properties (Alves et al., 2016). The interactions of anticancer drugs with cell membranes are of primary importance for drug transport, accumulation, and activity. Membranes can act as barriers, preventing or allowing drugs to diffuse freely. Additionally, anticancer drugs can change lipid membrane structure and properties. The insights gained from such studies can provide helpful information about the role of membranes in cancer-related mechanisms and drug interactions (Bourgaux and Couvreur, 2014). Structurally Normal cell membranes have an asymmetric lipid composition compared to symmetrical cancerous cell membranes. Additionally, in normal cells, the extracellular leaflet mainly consists of phosphatidylcholine (PC) and sphingolipids, and the intracellular leaflet is composed of phosphatidylethanolamine (PE) and phosphatidylserine (PS) lipids. The concentration of negatively charged PS lipids increases 5–9 times in the outer leaflet when normal cells are transformed into cancer cells, which is usually considered a biological signal. Consequently, cancer membranes have a less negative membrane potential than normal membranes (Sharma and Shah, 2021). The biophysical properties of the cell membrane are essential for understanding the interaction between small molecules and cancer cells. Therefore, studying the biophysical properties of membranes is a key role in developing strategies to overcome cancer (Peetla et al., 2013). Biophysical parameters such as fluidity, permeability, the force and energy in drug-membrane interactions, and the elasticity of the membrane impact drug effectiveness mechanisms (Li et al., 2018, Lee et al., 2008, Kim, 2023). Membrane fluidity is critical in determining the permeability of molecules to pass through the membrane (Zalba and Ten Hagen, 2017). This property is significant because reduced drug absorption in resistant cancer cells is associated with decreased membrane fluidity (Ramalho et al., 2022). Molecular dynamics (MD) simulations can provide valuable insights into membrane properties and the differences between lipid bilayers in normal and cancerous cells (Róg et al., 2021). This study aims to investigate the fluidity of normal and cancer cell membranes using MD simulations. First, we constructed normal and cancer membrane models. Each model contains five lipid types: DOPC(1,2-dioleoyl-sn-glycero-3-phosphocholine), DOPE (1,2-dioleoyl-sn-glycero-3- phosphoethanolamine), DOPG (1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)]), DOPS (1,2-dioleoyl-sn-glycero-3-phospho-L-serine), and CHL (cholesterol) (Almeida et al., 2021). We used the CHARMM-GUI to build the membranes and simulated them with GROMACS. Simulations were carried out 200 ns with the CHARMM36 force field and TIP3P water model. Lipid membrane fluidity could be related to lipid parameters such as order parameters and lateral diffusion coefficient. The lateral diffusion analysis is based on the mean square displacement (MSD) (Reddy et al., 2012). In the present study, we computed order and MSD parameters to investigate the changes in the bilayer's fluidity. Our results show decreased fluidity in cancer membranes.