Langmuir film approach with breast cancer and fibroblast cell membranes to explore their interaction with doxorubicin Pedrosa Bustos, María Graván, Pablo Peña-Martín, Jesús Navarro Marchal, Saul Abenhamar Marchal Corrales, Juan Antonio Galisteo González, Francisco Moncho Jordá, Arturo Gálvez Ruiz, María José Cell membranes Langmuir films Breast cancer This work was partially supported by the Biocolloid and Fluid Physics Group (ref. PAI-FQM115) of the University of Granada (Spain). The authors thank MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa” for funding PID2022-140151OB-C21 (to M.P., F.G.-G. and M.J.G.-R.) and PID2022-140151OBC22 (to J.A.M., J.P.-M. and S.N.-M.). A.M.-J. thanks the financial support provided by The Plan Estatal de Investigación Científica, Técnica y de Innovación (Project PID2022-136540NB-I00). M.P. thanks the FPU19/02045 fellowship, P.G. the FPU18/05336 fellowship, and J.P.-M. the PRE2019-088029, all funded by MCIN/AEI/10.13039/501100011033 and FSE. S.N.M. thanks the financial support provided by Sara Borrell grant (CD23/00142) co-funded by Instituto de Salud Carlos III (ISCIII) and FSE. This work has been done in the framework of the Doctoral Program in Physics and Space Sciences (B09/56/1) of the University of Granada. Funding for open access charge: Universidad de Granada / CBUA. Supplementary material. Supplementary document showing the molecular structure of the anticancer drug doxorubicin (DOX), the overlap of two compression–expansion cycles for fibroblast (FB) and MCF-7 membrane films, and the time-dependent variation of surface pressure for both films pre-compressed at 30 mN/m. https://ars.els-cdn.com/content/image/1-s2.0-S0021979725024129-mmc1.pdf Hypothesis The interaction between doxorubicin (DOX), a widely used chemotherapeutic agent, and cellular membranes significantly influences its therapeutic efficacy and selectivity. This study hypothesizes that membrane composition differences between breast cancer (MCF-7) and healthy fibroblast (FB) cells lead to distinct interactions with DOX. Experiments Langmuir films were created using isolated membranes from MCF-7 and FB cells, and surface pressure–area isotherms and compression-expansion cycles were recorded. Morphological features were evaluated through micro-Brewster angle microscopy (MicroBAM) and atomic force microscopy (AFM). DOX was introduced into the subphase to study its interaction with both membranes upon compression and over time in preformed films. Findings The high reproducibility of surface pressure-area isotherms and the minimal hysteresis in compression-expansion cycles confirm that cell membranes form stable Langmuir films. MCF-7 film isotherms exhibited larger molecular areas than FB films, indicating a more expanded state due to protein overexpression and lipid differences, but both displayed a similar surface compression modulus. Interaction with DOX differed between the MCF-7 and FB membranes, primarily due to the different electrostatic charges within the membrane components. DOX insertion increased hysteresis in both membrane types. At low pressures, DOX penetrated both films, whereas at high pressures it internalized more in FB films, likely due to hydrophobic interactions. DOX induces membrane aggregation, with more pronounced effects on MCF-7 membranes due to stronger electrostatic interactions. This study demonstrates the advantages of real cell membrane Langmuir films over lipid models in membrane-drug interaction studies. 2025-09-29T06:41:31Z 2025-09-29T06:41:31Z 2025-09-16 journal article M. Pedrosa et al., “Langmuir film approach with breast cancer and fibroblast cell membranes to explore their interaction with doxorubicin,” Journal of Colloid and Interface Science, vol. 703, p. 139020, 2026. https://doi.org/10.1016/j.jcis.2025.139020 https://hdl.handle.net/10481/106678 10.1016/j.jcis.2025.139020 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Elsevier