AFM detects the effects of acidic condition on the size and biomechanical properties of native/oxidized low-density lipoprotein

[Display omitted] •The effects of acidification on native/oxidized LDL are studied on the nanoscale by AFM.•LDL/oxLDL particles are smaller and softer at acidic pH vs. at neutral pH.•The protein/lipid changes are responsible for the biophysical changes of LDL/oxLDL.•Acidification may worsen tumori-/atherogenesis by changing LDL biophysical properties. Solution acidification exists under some physiological conditions (e.g. lysosomes in cells) and diseases (e.g. atherosclerosis, tumors, etc.). It is poorly understood whether and how acidification influences the size and biomechanical (stiffness and stickiness) properties of native Low-density lipoprotein (LDL) and its oxidized form (oxLDL) which plays a vital role in atherogenesis and tumorigenesis. Atomic force microscopy (AFM) evaluated that gradient acidification from pH 7.4 to pH 4.4 caused an expanding-first-and-then-shrinking decrease in size and a dramatic decrease in stiffness (but no statistically significant changes in stickiness) of LDL/oxLDL particles by influencing secondary/tertiary structures and lipid release detected by infrared spectral analysis and cholesterol detection, respectively. The smaller and softer characteristics of LDL/oxLDL at acidic conditions versus at the neutral pH partially explains the atherogenic role of acidification. The data may provide important information for a better understanding of LDL/oxLDL and some diseases (e.g. atherosclerosis and tumors).