Biology subjects

Baumann, K. N.

Publications and source records attributed to Baumann, K. N..

4 recordsLinked to original sources

bioRxiv2022

A Kinetic Map of the Influence of Biomimetic Lipid Membrane Models on Aβ42 Aggregation

The aggregation of the amyloid {beta} peptide (A{beta}) is one of the major molecular hallmarks of Alzheimers disease. Although A{beta} deposits have been mostly observed extracellularly, various studies have reported the presence of also intracellular A{beta} assemblies. Because these intracellular A{beta} aggregates might play a role in the onset and progression of Alzheimers disease, it is important to investigate their possible origins at different locations of the cell along the secretory pathway of the amyloid precursor protein (APP), from which A{beta} is derived by proteolytic cleavage. Since lipid bilayers have been shown to promote the aggregation of A{beta}, in this study we measure the effects of the lipid membrane composition on the in vitro aggregation kinetics of the 42-residue form of A{beta} (A{beta}42). By using small unilamellar vesicles modelling cellular membranes at different locations, including the inner and outer leaflets of the plasma membrane, late endosomes, the endoplasmic reticulum (ER), and the Golgi apparatus, we show that A{beta}42 aggregation is inhibited by the ER and Golgi membranes. These results provide a preliminary map of the possible effects of the membrane composition in different cellular locations on A{beta} aggregation, and suggest the presence of an evolutionary optimization of lipid composition to prevent the intracellular aggregation of A{beta}.

biophysics↗

bioRxiv2020

DNA-based nanocarriers to enhance the optoacoustic contrast of tumors in vivo

Optoacoustic tomography (OT) enables non-invasive deep tissue imaging of optical contrast at high spatio-temporal resolution. The applications of OT in cancer imaging often rely on the use of molecular imaging contrast agents based on near infrared dyes to enhance contrast at the tumor site. While these agents afford excellent biocompatibility and minimal toxicity, they present limited optoacoustic signal generation capability and rapid renal clearance, which can impede their tumor imaging efficacy. In this work, a synthetic strategy to overcome these limitations utilizing biodegradable DNA-based nanocarrier (DNA-NC) platforms is introduced. DNA-NCs enable the incorporation of near infrared dyes (in this case, IRDye 800CW) at precise positions to enable fluorescence quenching and maximize optoacoustic signal generation. Furthermore, these DNA-NCs show a prolonged blood circulation compared to the native fluorophores, facilitating tumor accumulation by the Enhanced Permeability and Retention (EPR) effect. In vivo imaging of tumor xenografts in mice following intravenous administration of DNA-NCs revealed enhanced OT signals at 24h when compared to free fluorophores, indicating promise for this method to enhance the optoacoustic signal generation capability and tumor uptake of clinically relevant near infrared dyes.

bioengineering↗

bioRxiv2017

Outperforming nature: synthetic enzyme built from DNA flips lipids of biological membranes at record rates

Mimicking enzyme function and increasing performance of naturally evolved proteins is one of the most challenging and intriguing aims of nanoscience. Here, we employ DNA nanotechnology to design a synthetic enzyme that substantially outperforms its biological archetypes. Consisting of only eight strands, our DNA nanostructure spontaneously inserts into biological membranes by forming a toroidal pore that connects the membranes inner and outer leaflets. The membrane insertion catalyzes spontaneous transport of lipid molecules between the bilayer leaflets, rapidly equilibrating the lipid composition. Through a combination of microscopic simulations and single-molecule experiments we find the lipid transport rate catalyzed by the DNA nanostructure to exceed 107 molecules per second, which is three orders of magnitude higher than the rate of lipid transport catalyzed by biological enzymes. Furthermore, we show that our DNA-based enzyme can control the composition of human cell membranes, which opens new avenues for applications of membrane-interacting DNA systems in medicine.

biophysics↗

bioRxiv2017

Photoacoustic molecular rulers based on DNA nanostructures

Molecular rulers that rely on the Forster resonance energy transfer (FRET) mechanism are widely used to investigate dynamic molecular processes that occur on the nanometer scale. However, the capabilities of these fluorescence molecular rulers are fundamentally limited to shallow imaging depths by light scattering in biological samples. Photoacoustic tomography (PAT) has recently emerged as a high resolution modality for in vivo imaging, coupling optical excitation with ultrasound detection. In this paper, we report the capability of PAT to probe distance-dependent FRET at centimeter depths. Using DNA nanotechnology we created several nanostructures with precisely positioned fluorophore-quencher pairs over a range of nanoscale separation distances. PAT of the DNA nanostructures showed distance-dependent photoacoustic signal generation and experimentally demonstrated the ability of PAT to reveal the FRET process deep within tissue mimicking phantoms. Further, we experimentally validated these DNA nanostructures as providing a novel and biocompatible strategy to augment the intrinsic photoacoustic signal generation capabilities of small molecule fluorescent dyes.

bioengineering↗