Red blood cell (RBC) membrane flickering arises from the interplay between thermal fluctuations, cytoskeletal elasticity, and metabolically driven non-equilibrium processes, making it a sensitive reporter of membrane mechanical state. Here, we introduce a computational microscopy framework that integrates bright-field morphometry with high-speed flickering spectroscopy to phenotype single-cell RBC mechanics under flavonoid exposure. As a proof of concept, human erythrocytes from a single donor were incubated with structurally distinct flavonoids (quercetin, apigenin, and rutin) prepared at sub-hemolytic concentrations, ensuring preservation of membrane integrity. Static shape descriptors and dynamic fluctuation spectra were extracted from segmented cell contours and analyzed through Fourier-mode decomposition to obtain compound-specific mechanical signatures. While gross morphology remained largely discocytic across conditions, flavonoid treatment induced reproducible alterations in flickering spectra and effective mechanical parameters, revealing distinct dynamical phenotypes that depend on flavonoid structure. In particular, aglycone flavonoids exhibited modulation patterns that differed from the glycosylated compound, consistent with differential membrane interactions. The combined analysis of geometry and dynamics provided enhanced discriminative power compared to either modality alone. These results establish computational microscopy as a sensitive, label-free approach to map compound-specific perturbations of RBC membrane mechanics and flickering, with potential applications in membrane biophysics, drug–membrane interaction screening, and single-cell mechanical phenotyping.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, marked by a survival rate of only 12%. Consequently, the exploration of novel therapeutic strategies becomes a critical clinical imperative. Among the genetic alterations contributing to PDAC, c-MYC overexpression arises due to upstream mutations, amplifications, and copy number alterations. c-MYC serves as a key regulator in the tumor’s metabolic reprogramming, playing a pivotal role in proliferation, migration, and metastasis. This study delves into the investigation of the role of the elongase ELOVL6 in c-MYC-induced cell transformation and its potential as a therapeutic target in PDAC. Here, we demonstrate that c-MYC regulates lipid elongation to promote cell transformation, offering a new avenue for therapeutic intervention. Initially, we show the direct regulation of ELOVLs expression by c-MYC in various PDAC mouse models and cell lines, elucidating its upregulation during transformation and tumor progression. Genetic or chemical inhibition of ELOVL6 results in decreased proliferation and migration, accompanied by alterations in fatty acid elongation. These changes in fatty acid composition led to modifications in membrane rigidity, permeability, and thickness, which collectively affect micropinocytosis and macropinocytosis. Importantly, we observe an increase in Abraxane uptake and a synergistic effect when combined with ELOVL6 interference in vitro . In vivo validation demonstrates that ELOVL6 inhibition significantly reduces tumor growth and enhances the response to Abraxane, thereby increasing overall survival. Altogether, these results position ELOVL6 as a promising therapeutic target in the treatment of PDAC.