DNA adopts different conformations based on its environment. We reveal conditions that either preserve the DNA’s physiological B-conformation, even upon its placement in UHV, or lead to a partial B-form to A-form reorganization upon DNA’s deposition on a surface. We use high-resolution AFM to image DNA with a well-defined number of base pairs deposited on mica. To enable the DNA’s adhesion, we either add divalent cations to the DNA solution or functionalize the surface with a silane layer. The contour length of DNA on the silane is always in perfect agreement with the B-form conformation, whereas cation-deposited DNA is always, in some cases up to 20% shorter. We varied the equilibration time, the DNA length, and sequence and compared nicked to non-nicked molecules, thus identifying several factors controlling the DNA’s length. We performed TERS measurements confirming spectroscopically that cation-deposited DNA undergoes a partial B-form to A-form conformational transition upon drying and pinpointed positions along the DNA where this transition was more probable, namely the ends of the molecules. Controlling the conformation of DNA is essential for its nanotechnology applications such as nanotemplating. Our findings could also shed a whole new light on DNA polymer physics, the mechanisms of DNA binding to surfaces, or the abundant contradictory data on DNA’s electrical behavior.

BackgroundA wide class of human diseases and neurodegenerative disorders, such as Alzheimer’s disease, is due to the failure of a specific peptide or protein to keep its native functional conformational state and to undergo a conformational change into a misfolded state, triggering the formation of fibrillar cross-β sheet amyloid aggregates. During the fibrillization, several coexisting species are formed, giving rise to a highly heterogeneous mixture. Despite its fundamental role in biological function and malfunction, the mechanism of protein self-assembly and the fundamental origins of the connection between aggregation, cellular toxicity and the biochemistry of neurodegeneration remains challenging to elucidate in molecular detail. In particular, the nature of the specific state of proteins that is most prone to cause cytotoxicity is not established.Methods:In the present review, we present the latest advances obtained by Atomic Force Microscopy (AFM) based techniques to unravel the biophysical properties of amyloid aggregates at the nanoscale. Unraveling amyloid single species biophysical properties still represents a formidable experimental challenge, mainly because of their nanoscale dimensions and heterogeneous nature. Bulk techniques, such as circular dichroism or infrared spectroscopy, are not able to characterize the heterogeneity and inner properties of amyloid aggregates at the single species level, preventing a profound investigation of the correlation between the biophysical properties and toxicity of the individual species.Conclusion:The information delivered by AFM based techniques could be central to study the aggregation pathway of proteins and to design molecules that could interfere with amyloid aggregation delaying the onset of misfolding diseases.

We show that in Pr 0.5 La 0.2 Ca 0.3 MnO 3 /YBa 2 Cu 3 O 7 (PLCMO/YBCO) multilayers the low temperature state of YBCO is very resistive and resembles that of a granular superconductor or a frustrated Josephson-junction network. Notably, a coherent superconducting response can be restored with a large magnetic field which also suppresses the charge-orbital order in PLCMO. This coincidence suggests that the granular superconducting state of YBCO is induced by the charge-orbital order of PLCMO. The coupling mechanism and the nature of the induced inhomogeneous state in YBCO remain to be understood. [6,7] for which the magnetic field compensates a negative exchange field from magnetic ions, thereby reducing the pair breaking (Jacarino-Peter effect) [8], or suppresses detrimental magnetic fluctuations [9]. A reentrance of SC was also reported in Zn nanowires where the field seems to reduce quantum fluctuations by generating dissipative quasiparticles [10,11].In the following, we show that yet another kind of these rare cases can be found in cuprate/manganite multilayers. Here the magnetic field restores a coherent SC state in a thin YBa 2 Cu 3 O 7 (YBCO) layer, most likely since it suppresses an interaction with the neighboring Pr 0.5 La 0.2 Ca 0.3 MnO 3 (PLCMO) layers that is detrimental to a macroscopic SC coherence. PLCMO exhibits a combined charge-orbital order [12] and an antiferromagnetic (AF) order with a weak ferromagnetic (FM) component that arises either from a spin canting or phase segregation. A large magnetic field suppresses this charge-orbital ordered AF state towards an itinerant FM state [12]. Surprisingly, the latter state of PLCMO is less detrimental to the SC in YBCO than the former.PLCMO (20 nm)/YBCO (7, 9, and 20 nm)/PLCMO (20 nm) trilayers and PLCMO(20 nm)-YBCO(3.5 and 4.5 nm) bilayers were grown on La 0.3 Sr 0.7 Al 0.65 Ta 0.35 O 3 substrates by pulsed * benjamin

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Interaction of the atomic force microscopy (AFM) tip with the sample can be invasive for soft samples. Frequency Modulation (FM) AFM is gentler because it allows scanning in the non-contact regime where only attractive forces exist between the tip and the sample, and there is no sample compression. Recently, FM-AFM was used to resolve the atomic structure of single molecules of pentacene and of carbon nanotubes. We are testing similar FM-AFM-based approaches to study biological samples. We present FM-AFM experiments on dsDNA deposited on 3-aminopropyltriethoxysilane modified mica in ultra high vacuum. With flexible samples such as DNA, the substrate flatness is a sub-molecular resolution limiting factor. Non-contact topographic images of DNA show variations that have the periodicity of the right handed helix of B-form DNA - this is an unexpected result as dehydrated DNA is thought to assume the A-form structure. Frequency shift maps at constant height allow working in the non-monotonic frequency shift range, show a rich contrast that changes significantly with the tip-sample separation, and show 0.2 to 0.4 nm size details on DNA. Frequency shift versus distance curves acquired on DNA molecules and converted in force curves show that for small molecules (height < 2.5 nm), there is a contribution to the interaction force from the substrate when the tip is on top of the molecules. Our data shine a new light on dehydrated and adsorbed DNA behavior. They show a longer tip-sample interaction distance. These experiments may have an impact on nanotechnological DNA applications in non-physiological environments such as DNA based nanoelectronics and nanotemplating.