In acute myeloid leukemia (AML), disease relapse is often observed because of therapy-resistant leukemic stem cells that re-initiate the disease. Leukemic stem cells can tightly associate with mesenchymal stromal cells inside the bone marrow, which is considered to further drive drug resistance. Here, the cell membrane of bone marrow stromal cells is used to prepare cell membrane nanoparticles and study their interactions with AML cells. Cell membrane liposomes (CM-Liposomes) of different charge are prepared and either used directly, or after deposition on silica cores to modulate nanoparticle mechanical properties. Nanoparticle size, zeta potential and coating efficiency are analyzed by dynamic light scattering (DLS) and cryo electron microscopy (Cryo-EM) imaging. Atomic force microscopy (AFM) is used to characterize the mechanical properties of CM-Liposomes and confirm bilayer deposition on silica cores. Finally, uptake by leukemic cells is determined. No difference in uptake is found between soft CM-Liposomes and liposomes of the same composition without membrane components. Instead, after deposition on a rigid core, uptake is higher for the cell membrane particles. Preliminary results on primary cells from leukemia patients confirm this observation. These results show that nanoparticle rigidity strongly affects the interaction between cell membrane nanoparticles and the targeted cells.