The experimental work by Sabnis et al. marked a pivotal point in the optimization of the IL chemistry, focusing on enhancing protein expression and subsequent fusion efficacy. From the well-established MC3 lipid, they derived nine additional ILs. Compared to MC3, one derivative performed worse (Lipid 2), while others exhibited significantly enhanced performance (such as Lipid 10) in terms of protein expression. The distinctions between Lipid 2, 10, and MC3 lie in increasing saturation and branching of the tails, coupled with the introduction of an additional ester group, which makes Lipid 10 more biodegradable . In an attempt to reproduce these experimental trends, we performed a fusion PMF assay with bilayers mimicking LNP formulations (IL:CHOL:DSPC at 50:40:10 mol% ratio), were MC3, Lipid 2, or Lipid 10 where the ILs studied, and a plasma membrane , as mentioned above.