ORCID Profile
0000-0001-7328-0400
Current Organisation
Uppsala University
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Springer Science and Business Media LLC
Date: 11-02-2015
DOI: 10.1038/NCOMMS6704
Abstract: There exists a conspicuous gap of knowledge about the organization of life at mesoscopic levels. Ultra-fast coherent diffractive imaging with X-ray free-electron lasers can probe structures at the relevant length scales and may reach sub-nanometer resolution on micron-sized living cells. Here we show that we can introduce a beam of aerosolised cyanobacteria into the focus of the Linac Coherent Light Source and record diffraction patterns from in idual living cells at very low noise levels and at high hit ratios. We obtain two-dimensional projection images directly from the diffraction patterns, and present the results as synthetic X-ray Nomarski images calculated from the complex-valued reconstructions. We further demonstrate that it is possible to record diffraction data to nanometer resolution on live cells with X-ray lasers. Extension to sub-nanometer resolution is within reach, although improvements in pulse parameters and X-ray area detectors will be necessary to unlock this potential.
Publisher: Springer Science and Business Media LLC
Date: 08-2016
Abstract: Structural studies on living cells by conventional methods are limited to low resolution because radiation damage kills cells long before the necessary dose for high resolution can be delivered. X-ray free-electron lasers circumvent this problem by outrunning key damage processes with an ultra-short and extremely bright coherent X-ray pulse. Diffraction-before-destruction experiments provide high-resolution data from cells that are alive when the femtosecond X-ray pulse traverses the s le. This paper presents two data sets from micron-sized cyanobacteria obtained at the Linac Coherent Light Source, containing a total of 199,000 diffraction patterns. Utilizing this type of diffraction data will require the development of new analysis methods and algorithms for studying structure and structural variability in large populations of cells and to create abstract models. Such studies will allow us to understand living cells and populations of cells in new ways. New X-ray lasers, like the European XFEL, will produce billions of pulses per day, and could open new areas in structural sciences.
Publisher: Springer Science and Business Media LLC
Date: 17-11-2014
Publisher: SPIE
Date: 17-10-2012
DOI: 10.1117/12.929294
Publisher: The Optical Society
Date: 20-01-2015
DOI: 10.1364/OE.23.001213
Publisher: International Union of Crystallography (IUCr)
Date: 21-10-2015
DOI: 10.1107/S2052252515016887
Abstract: During the last five years, serial femtosecond crystallography using X-ray laser pulses has been developed into a powerful technique for determining the atomic structures of protein molecules from micrometre- and sub-micrometre-sized crystals. One of the key reasons for this success is the `self-gating' pulse effect, whereby the X-ray laser pulses do not need to outrun all radiation damage processes. Instead, X-ray-induced damage terminates the Bragg diffraction prior to the pulse completing its passage through the s le, as if the Bragg diffraction were generated by a shorter pulse of equal intensity. As a result, serial femtosecond crystallography does not need to be performed with pulses as short as 5–10 fs, but can succeed for pulses 50–100 fs in duration. It is shown here that a similar gating effect applies to single-molecule diffraction with respect to spatially uncorrelated damage processes like ionization and ion diffusion. The effect is clearly seen in calculations of the diffraction contrast, by calculating the diffraction of the average structure separately to the diffraction from statistical fluctuations of the structure due to damage (`damage noise'). The results suggest that sub-nanometre single-molecule imaging with 30–50 fs pulses, like those produced at currently operating facilities, should not yet be ruled out. The theory presented opens up new experimental avenues to measure the impact of damage on single-particle diffraction, which is needed to test damage models and to identify optimal imaging conditions.
Publisher: The Optical Society
Date: 29-01-2014
DOI: 10.1364/OE.22.002497
Publisher: Springer Science and Business Media LLC
Date: 26-02-2018
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7CP07267H
Abstract: Simulations of the explosions of single particles imaged with X-ray lasers show that ions ejected from the fragmented s les can be used to determine the spatial orientation of the particle at the time of interaction.
Publisher: AIP Publishing
Date: 07-2019
DOI: 10.1063/1.5098309
Abstract: The prospect of single particle imaging with atomic resolution is one of the scientific drivers for the development of X-ray free-electron lasers. The assumption since the beginning has been that damage to the s le caused by intense X-ray pulses is one of the limiting factors for achieving subnanometer X-ray imaging of single particles and that X-ray pulses need to be as short as possible. Based on the molecular dynamics simulations of proteins in X-ray fields of various durations (5 fs, 25 fs, and 50 fs), we show that the noise in the diffracted signal caused by radiation damage is less than what can be expected from other sources, such as s le inhomogeneity and X-ray shot-to-shot variations. These findings show a different aspect of the feasibility of high-resolution single particle imaging using free-electron lasers, where employing X-ray pulses of longer durations could still provide a useful diffraction signal above the noise due to the Coulomb explosion.
Publisher: International Union of Crystallography (IUCr)
Date: 19-08-2021
DOI: 10.1107/S1600577521007657
Abstract: X-rays are routinely used for structural studies through scattering, and femtosecond X-ray lasers can probe ultrafast dynamics. We aim to capture the femtosecond dynamics of liquid s les using simulations and deconstruct the interplay of ionization and atomic motion within the X-ray laser pulse. This deconstruction is resolution dependent, as ionization influences the low momentum transfers through changes in scattering form factors, while atomic motion has a greater effect at high momentum transfers through loss of coherence. Our methodology uses a combination of classical molecular dynamics and plasma simulation on a protic ionic liquid to quantify the contributions to the scattering signal and how these evolve with time during the X-ray laser pulse. Our method is relevant for studies of organic liquids, biomolecules in solution or any low- Z materials at liquid densities that quickly turn into a plasma while probed with X-rays.
Publisher: Springer Science and Business Media LLC
Date: 08-2016
Abstract: Ultra-intense femtosecond X-ray pulses from X-ray lasers permit structural studies on single particles and biomolecules without crystals. We present a large data set on inherently heterogeneous, polyhedral carboxysome particles. Carboxysomes are cell organelles that vary in size and facilitate up to 40% of Earth’s carbon fixation by cyanobacteria and certain proteobacteria. Variation in size hinders crystallization. Carboxysomes appear icosahedral in the electron microscope. A protein shell encapsulates a large number of Rubisco molecules in paracrystalline arrays inside the organelle. We used carboxysomes with a mean diameter of 115±26 nm from Halothiobacillus neapolitanus . A new aerosol s le-injector allowed us to record 70,000 low-noise diffraction patterns in 12 min. Every diffraction pattern is a unique structure measurement and high-throughput imaging allows s ling the space of structural variability. The different structures can be separated and phased directly from the diffraction data and open a way for accurate, high-throughput studies on structures and structural heterogeneity in biology and elsewhere.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 11-01-2013
Abstract: A bottleneck in x-ray crystallography is the growth of well-ordered crystals large enough to obtain high-resolution diffraction data within an exposure that limits radiation damage. Serial femtosecond crystallography promises to overcome these constraints by using short intense pulses that out-run radiation damage. A stream of crystals is flowed across the free-electron beam and for each pulse, diffraction data is recorded from a single crystal before it is destroyed. Redecke et al. (p. 227 , published online 29 November see the Perspective by Helliwell ) used this technique to determine the structure of an enzyme from Trypanosoma brucei , the parasite that causes sleeping sickness, from micron-sized crystals grown within insect cells. The structure shows how this enzyme, which is involved in degradation of host proteins, is natively inhibited prior to activation, which could help in the development of parasite-specific inhibitors.
No related grants have been discovered for Nicusor Timneanu.