2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
April 18th, 2025
Version: 2
The University of Texas Southwestern Medical Center
biophysics
biorxiv

Altair-LSFM: A High-Resolution, Easy-to-Build Light-Sheet Microscope for Sub-Cellular Imaging

Haug, J.Open in Google Scholar•Gałecki, S.Open in Google Scholar•Dean, K. M.Open in Google Scholar

Although several open-source, easy-to-assemble light-sheet microscope platforms already exist--such as mesoSPIM, OpenSPIM, and OpenSpin--they are primarily optimized for imaging large specimens and lack the resolution required to visualize sub-cellular organelles or cytoskeletal architectures. Conversely, commercial systems like Lattice Light-Sheet Microscopy offer improved resolution but are complex, expensive, and alignment-intensive. To address this gap, we developed Altair-LSFM, a high-resolution, open-source, sample-scanning light-sheet microscope specifically designed for sub-cellular imaging. By optimizing the optical pathway in silico, we created a custom baseplate with precisely positioned dowel pins to simplify alignment and assembly. The system integrates streamlined optoelectronics and optomechanics with seamless operation through our open-source software, navigate. Altair-LSFM achieves lateral and axial resolutions of approximately 235 nm and 350 nm, respectively, across a 266-micron field of view after deconvolution. We validate the systems capabilities by imaging sub-diffraction fluorescent nanospheres and visualizing fine structural details in mammalian cells, including microtubules, actin filaments, nuclei, and Golgi apparatus.

Similar Papers

biorxiv
Sun Apr 20 2025
Dynamic Pathway of Guanidine-III Riboswitch Folding Revealed by Single-Molecule FRET: Mg2+-Assisted Preorganization and Ligand-Induced Kinetic Trapping
Riboswitches are structured RNA elements that regulate gene expression by sensing and binding small molecules. The guanidine-III riboswitch, a critical bacterial regulator responding to guanidine toxicity, undergoes precise conformational changes that remain poorly characterized at a dynamic, mechanistic level. In this study, we employed single-molecule Forster Resonance Energy Transfer (smFRET) c...
Jiang, M.
•
Bian, Y.
•
Zou, L.
•
Liu, T.
...•
Pan, H.
biorxiv
Sat Apr 19 2025
Phosphorylation of Ser81 in human AGT reversibly inactivate enzyme function and mimics catalytic defects of certain PH1-causing mutations
Phosphorylation is fundamental to modulate protein function and stabilty. There have detected about 300000 site-specic Phosphorylation sites in over 20000 human proteins. However, only 5% of the sites have been experimenrally characterized. In this work, we investigated a phosphorylation event in AGT, an important enzyme due to its detoxifying role of glyoxylate and hundreds of mutations cause a r...
Milosevic, S.
•
Cano, M.
•
Salido, E.
•
Mesa, N.
•
Pey, A. l.
biorxiv
Sat Apr 19 2025
From Decay to Rhythm: Sustained Biological Oscillators Require More Than Chemistry Alone
Many biological systems exhibit rhythmic oscillatory dynamics, yet it is shown that chemical reaction systems governed by Markovian dynamics cannot generate long-lasting oscillations. To overcome this limitation, we propose a general mechanism that couples a Markovian system to at least one other degree of freedom, such as a mechanical system, to achieve sustained oscillations with a desired frequ...
Wu, Y.
•
Sun, S.
biorxiv
Sat Apr 19 2025
Mechanistic Insight of Tardigrade Anhydrobiosis via Protein Structural Analysis
Tardigrades are microscopic animals exhibiting exceptional tolerance to extreme environmental stresses such as desiccation. Hence, they provide unique solutions to biological preservation, anti-aging, and interstellar travel. Recent studies show that various cytoplasmic and secretory abundant heat soluble proteins (CAHSs and SAHSs) enable tardigrades to survive complete dehydration and revive upon...
Zhang, C.
biorxiv
Sat Apr 19 2025
Lenacapavir-induced Lattice Hyperstabilization is Central to HIV-1 Capsid Failure at the Nuclear Pore Complex and in the Cytoplasm
Lenacapavir (LEN) is the first HIV-1 capsid inhibitor approved for clinical use.It inhibits multiple steps of the viral life cycle; however, the molecular details of the effect of LEN on capsid structure and the mechanistic steps of the inhibition are not understood. Recent studies show that intact cone-shaped capsids and capsids with LEN-induced breaks can dock at nuclear pore complexes (NPC), bu...
Hudait, A.
•
Burdick, R. C.
•
Bare, E. K.
•
Pathak, V. K.
•
Voth, G. A.
biorxiv
Fri Apr 18 2025
Multivalent interaction induces phase separation and formation of more toxic aggregates of α-syn in a yeast model of Parkinson's disease
The process of protein phase separation, particularly in the context of intrinsically disordered proteins, has been extensively studied for its implications in several neuro-degenerative diseases. Although the mechanism of protein phase separation and the involved molecular grammar have been well explored under in vitro conditions, the focus is now shifting towards developing more complex models o...
Chattopadhyay, K.
•
Jain, R.
•
Sharavanakkumar, S.
biorxiv
Fri Apr 18 2025
Functional relevance of CASP16 nucleic acid predictions as evaluated by structure providers
Accurate biomolecular structure prediction enables the prediction of mutational effects, the speculation of function based on predicted structural homology, the analysis of ligand binding modes, experimental model building and many other applications. Such algorithms to predict essential functional and structural features remain out of reach for biomolecular. Here, we report quantitative and quali...
Kretsch, R. C.
•
Albrecht, R.
•
Andersen, E. S.
•
Chen, H.-A.
...•
Kryshtafovych, A.
biorxiv
Fri Apr 18 2025
Statistical Molecular Interaction Fields: A Fast andInformative Tool for Characterizing RNA and ProteinBinding Pockets
Developing a physical understanding of the interactions between a macromolecular target and its ligands is a crucial step in structure-based drug design. Although many tools exist to characterize protein-binding pockets in silico, this is not yet the case for RNA, which has only recently been recognized as a suitable target for small ligands. Molecular Interaction Fields (MIF) are a useful tool to...
Barquero Morera, D.
•
Mattiotti, G.
•
Kocev, A.
•
Rousselot, A.
...•
Pasquali, S.
biorxiv
Fri Apr 18 2025
AMOEBA Polarizable Molecular Dynamics Simulations of Guanine Quadruplexes: from the c-Kit Proto-oncogene to HIV-1
Long oligomer sequences, rich in guanine and cytosine, such as c-kit1 and the HIV-1 LTR-III sequence, are prevalent in oncogenes and retroviruses and play crucial roles in cancer. Understanding the conformational dynamics of such guanine quadruplexes and identifying druggable regions are therefore essential for developing new inhibition strategies. In this study, we used extensive AMOEBA polarizab...
El Ahdab, D. S.
•
Lagardere, L.
•
Hobaika, Z.
•
Jaffrelot Inizan, T.
...•
Piquemal, J.-P.