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1. Investigation of Protein/Lipid Interactions via Scanning Probe Acceleration Microscopy: Theory and Experiment

   https://doi.org/10.1115/DETC2012-70228  

   Legleiter, Justin; Burke, Kathleen A.; Yates, Elizabeth A. (August 2012, ASME 2012 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference)

   There is great interest in the application of proximal probe techniques to simultaneously image and measure mechancial properties of surfaces with nanoscale spatial resolution. There have been several innovations in generating time-resolved force interaction between the tip and surface while acquiring a tapping mode AFM image. These tip/sample forces contain information regarding mechanical properties of surfaces in an analogous fashion to a force curve experiment. Here, we demonstrate, via simulation, that the maximum and minimum tapping forces change with respect to the Young’s modulus and adhesiveness of a surface, but the roughness of the surfaces has no effect on the tapping forces. Using these changes in tapping forces, we determine the mechanical changes of a lipid membrane after exposure to a huntingtin exon1 (htt exon1) protein with an expanded polyglutamine (polyQ) domain. Expanded polyQ domains in htt is associated with Huntington’s disease, a genetic neurodegenerative disorder. The htt exon1 protein caused regions of increased surface roughness to appear in the lipid membrane, and these areas were associated with decreased elasticity and adhesion to the AFM probe. 

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2. Multiscale compression-induced restructuring of stacked lipid bilayers: From buckling delamination to molecular packing

   https://doi.org/10.1371/journal.pone.0275079  

   Porras-Gómez, Marilyn; Kim, Hyunchul; Dronadula, Mohan Teja; Kambar, Nurila; Metellus, Christopher J.; Aluru, Narayana R.; van der Zande, Arend; Leal, Cecília (December 2022, PLOS ONE)

   Johnson, Colin (Ed.)

   Lipid membranes in nature adapt and reconfigure to changes in composition, temperature, humidity, and mechanics. For instance, the oscillating mechanical forces on lung cells and alveoli influence membrane synthesis and structure during breathing. However, despite advances in the understanding of lipid membrane phase behavior and mechanics of tissue, there is a critical knowledge gap regarding the response of lipid membranes to micromechanical forces. Most studies of lipid membrane mechanics use supported lipid bilayer systems missing the structural complexity of pulmonary lipids in alveolar membranes comprising multi-bilayer interconnected stacks. Here, we elucidate the collective response of the major component of pulmonary lipids to strain in the form of multi-bilayer stacks supported on flexible elastomer substrates. We utilize X-ray diffraction, scanning probe microscopy, confocal microscopy, and molecular dynamics simulation to show that lipid multilayered films both in gel and fluid states evolve structurally and mechanically in response to compression at multiple length scales. Specifically, compression leads to increased disorder of lipid alkyl chains comparable to the effect of cholesterol on gel phases as a direct result of the formation of nanoscale undulations in the lipid multilayers, also inducing buckling delamination and enhancing multi-bilayer alignment. We propose this cooperative short- and long-range reconfiguration of lipid multilayered films under compression constitutes a mechanism to accommodate stress and substrate topography. Our work raises fundamental insights regarding the adaptability of complex lipid membranes to mechanical stimuli. This is critical to several technologies requiring mechanically reconfigurable surfaces such as the development of electronic devices interfacing biological materials. 

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3. Photo-induced force microscopy (PiFM) – principles and implementations

   https://doi.org/10.1039/D2CS00052K  

   Sifat, Abid Anjum; Jahng, Junghoon; Potma, Eric O. (June 2022, Chemical Society Reviews)

   Photo-induced force microscopy (PiFM) is a scan probe technique that offers images with spectroscopic contrast at a spatial resolution in the nanometer range. PiFM utilizes the non-propagating, enhanced near field at the apex of a sharp tip to locally induce a polarization in the sample, which in turn produces an additional force acting on the cantilevered tip. This photo-induced force, though in the pN range or less, can be extracted from the oscillation properties of the cantilever, thus enabling the generation of photo-induced force maps. Since its inception in 2010, the PiFM technique has grown into a useful nano-spectrocopic tool that has expanded its reach in terms of imaging capabilities and applications. In this review, we present various technical implementations of the PiFM approach. In addition, we discuss the physical origin of the PiFM signal, highlighting the contributions from dipole–dipole forces as well as forces that derive from photo-thermal processes. 

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4. Control of quality factor of atomic force microscopy cantilever by cavity optomechanical effect

   https://doi.org/10.35848/1347-4065/ad39f6  

   Austin-Bingamon, Noah; D_C, Binod; Miyahara, Yoichi (April 2024, Japanese Journal of Applied Physics)

   Abstract The effective quality factor of the cantilever plays a fundamental role in dynamic mode atomic force microscopy. Here we present a technique to modify the quality factor of an atomic force microscopy cantilever within a Fabry–Perot optical interferometer. The experimental setup uses two separate laser sources to detect and excite the oscillation of the cantilever. While the intensity modulation of the excitation laser drives the oscillation of the cantilever, the average intensity can be used to modify the quality factor via optomechanical force without changing the fiber-cantilever cavity length. The technique enables users to optimize the quality factor for different types of measurements without influencing the deflection measurement sensitivity. An unexpected frequency shift was observed and modelled as temperature dependence of the cantilever’s Young’s modulus, which was validated using finite element simulation. The model was used to compensate for the thermal frequency shift. The simulation provided relations between optical power, temperature, and frequency shift. 

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5. Tunable Electrostatic Interactions of Lipid-Coated Quantum Dots with Biological Membranes

   Morgenstein, Lion; Huang-Zhu, Carlos A; Yudovich, Shimon; Grupi, Asaf; Van_Lehn, Reid C; Weiss, Shimon (August 2026, Langmuir)

   Surface functionalization of inorganic quantum dot nanoparticles is of great interest in the application of these materials toward a wide range of biological applications where membrane interactions are critical. The use of amphiphilic lipids to functionalize the surfaces of quantum dots represents a promising alternative to produce water-soluble and membrane-active materials with facile tuning of the quantum dot's surface properties. Here, we demonstrate an experimental approach that yields lipid-coated quantum dots with highly tunable surface charge by controlling the concentration of cationic lipids during preparation. Through fluorescence-activated cell sorting assays, we show that these cationic lipid-coated quantum dots can enhance membrane interactions and increase membrane labeling density in live HEK293 cells. We further employed coarse-grained molecular dynamics simulations to model the lipid self-assembly process using an implicit solvent force field and subsequently model the adsorption of lipid-coated quantum dots to model membranes. Our simulations show that we can control the effective surface charge of lipid-coated quantum dots and influence the strength of adsorption to oppositely charged lipid membranes, a process that is mediated by the release of counterions at the quantum dot-membrane interface. This work supports the future development of biocompatible and water-soluble inorganic nanoparticles with highly tunable surfaces, and provides mechanistic insight into how different lipids can influence nanoparticle-membrane interactions at a molecular scale. 

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