THE BOERSMA LAB

Welcome to the website of the Arnold Boersma Lab. We are embedded within the DWI-Leibniz Institute for Interactive Materials, in Aachen, Germany.

The Boersma group works in the area of chemical biology, synthetic biochemistry, synthetic chemistry and biochemistry. We engineer new proteins, small molecules, oligonucleotides, as well as larger cell-like systems for fundamental biological understanding but also with specific applications in mind. Applications range from medical tools (diagnosis, screening and/or treating the disease) to materials and devices. The group has especially a strong record of accomplishment on the design of FRET-based protein probes for macromolecular crowding in diverse living and nonliving systems and for ionic strength measurements. Current interests lie in the development of novel probes and cell-like systems to detect novel parameters in fields that range from biology to material science.

RESEARCH

DESIGNING NEW FRET SENSORS TO UNDERSTAND THE INTRACELLULAR ENVIRONMENT

The interior of the cells is obviously not like dilute buffer. Yet, traditionally most biochemistry experiments have been performed in dilute buffer. To understand how the interior of the cell influences biochemical processes, such as biocatalysis and organization of the biopolymers, we need to know what the important parameters in the cell are, and quantify their contribution to the intracellular organization.

By creative design, we developed a series FRET sensors for macromolecular crowding and the ionic strength: Cells are crowded with macromolecules that occupy space, generating a force that influences the organization of biomolecules in cells. The crowding sensors compress akin a polymer in crowded solutions. The sensors provide a readout for the excluded volume in bacteria, yeasts, and mammalian cells. Our efforts are towards improving these sensors, as well as applying them in different species. Further, we apply the sensors in dynamic soft materials.

IONIC STRENGTH SENSING

The other sensor that we developed measures the ionic strength. The ionic strength is important for anything charged, which includes pretty much every molecule in the living cell (apart from a few small molecules). Our FRET-based ionic strength sensor allows to determine the ionic strength inside living cells, with all the advantages of FRET-based genetically-encoded sensors, such as high spatiotemporal resolution, and easy targeting to different compartments.

LIFE-LIKE SYSTEMS, INFORMATION TRANSFER, DIAGNOSTIC TOOLS, AND MORE

We will provide more information in due course.

NEWS

SARA PUBLISHES IN ELIFE ON PHYSICAL CHEMICAL PARAMETERS IN YEAST DURING AGING

October 10, 2020

With our optimized crowding sensor in yeast in a dedicated microfluidics device, we show that crowding is relatively stable during yeast aging, contrasting with our initial expectations, with the note that longer-lived cells show higher crowding stability. On larger length scales (at least more than the 8-nm crowding sensor), we show with CLEM (correlative light-electron microscopy) that there are drastic changes in the organellar volume fractions. We tentatively name this organellar crowding to distinguish the µm-scale crowding with nm-scale macromolecular crowding. Using pHluorin, a green fluorescent protein sensitive to the pH, we observe small but significant acidification of the cytoplasm, which decreases sharply after senescence. We hoped to show that several physical and chemical parameters drift during aging, and the levels at which they arrive should be considered when describing molecular events in old cells

ILARIA, MENG-RUO, AND NUNO JOIN THE LAB

August 8, 2020

We are stoked to be joined by three new members in the lab at the same time (partially due to delays induced by Covid...). Ilaria will perform her master thesis on synthetic cells, while Meng-Ruo will do his postdoc studies on chemistry on proteins and in cells, and Nuno will perform his postdoc studies on the intracellular physicochemical properties. The lab is getting ever more busy and vibrant!

SELECTED IN RISING STARS IN SENSIGN VIRTUAL ISSUE

August 8, 2020

We are honored to be included in the rising stars of sensing virtual issue of ACS Sensors. This is a great recognition of the work the team has been performing in the last few years. You can find the issue here.

PROTOCOL ON CROWDING MEASUREMENTS

July 26, 2020

Sara wrote a very informative chapter in Methods in Molecular Biology on how to perform accurate crowding measurements inside yeast cells. This protocol is included in a topic on The Nucleus, edited by Ronald Hancock. One of our main messages that we convey in our notes is that cells need to be treated gently because the organization in their interior is affected relatively quickly!

MEET THE TEAM

ARNOLD BOERSMA

Principle Investigator

Dr. Arnold J. Boersma studied chemistry at the University of Groningen (The Netherlands) where he also pursued his graduate studies in the group of Prof. Ben L. Feringa (Nobel Laureate, 2016) and Prof. Gerard Roelfes. Here, he developed a new concept in catalysis by using DNA as an asymmetric catalyst. For this research, he was awarded the KNCV Catalysis prize for the best PhD thesis on catalysis in the Netherlands. He then worked as a postdoctoral fellow at Oxford University in the group of Prof. Hagan Bayley, funded by an NWO Rubicon grant. Here, he became an expert in protein engineering and lipid membranes. In 2012, he returned to the University of Groningen to become an independent researcher with an NWO Veni fellowship. Here, he developed novel probes to detect the physicochemical properties in various types of cells. Based on these research achievements he was awarded an NWO Vidi fellowship in 2016 to become a group leader. He joined the DWI-Leibniz Institute for Interactive Materials in August 2018, where he obtained the ERC Consolidator grant in 2020.

PUBLISHED WORK

2020

Engineering Crowding Sensitivity into Protein Linkers.

Pittas T, Zuo W, Boersma AJ.

Methods Enzymol. 2020 doi: 10.1016/bs.mie.2020.09.007

Controlling Optical and Catalytic Activity of Genetically Engineered Proteins by Ultrasound.

Zhou Y, Huo S, Loznik M, Göstl R, Boersma AJ, Herrmann A.

Angew Chem Int Ed Engl. 2020 Oct 26. doi: 10.1002/anie.202010324. Online ahead of print.

A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast.

Mouton SN, Thaller DJ, Crane MM, Rempel IL, Terpstra OT, Steen A, Kaeberlein M, Lusk CP, Boersma AJ, Veenhoff LM.

Elife. 2020 Sep 29;9:e54707. doi: 10.7554/eLife.54707.

Macromolecular Crowding Measurements with Genetically Encoded Probes Based on Förster Resonance Energy Transfer in Living Cells.

Mouton SN, Veenhoff LM, Boersma AJ.

Methods Mol Biol. 2020; 2175:169-180. doi: 10.1007/978-1-0716-0763-3_12.

The more the merrier: effects of macromolecular crowding on the structure and dynamics of biological membranes.

Löwe M, Kalacheva M, Boersma AJ, Kedrov A.

FEBS J. 2020 May 28. doi: 10.1111/febs.15429. Online ahead of print.

Modular and Versatile trans-Encoded Genetic Switches.

Paul A, Warszawik EM, Loznik M, Boersma AJ, Herrmann A

Angew Chem Int Ed Engl. 2020 Apr 30. doi: 10.1002/anie.202001372. Online ahead of print.

FRET Analysis of Ionic Strength Sensors in the Hofmeister Series of Salt Solutions Using Fluorescence Lifetime Measurements

Miller RC, Aplin CP, Kay TM, Leighton R, Libal C, Simonet R, Cembran A, Heikal AA, Boersma AJ, Sheets ED

J Phys Chem B. 2020 Apr 30;124(17):3447-3458. doi: 10.1021/acs.jpcb.9b10498. Epub 2020 Apr 16.

Supercharged Proteins and Polypeptides.

Ma C, Malessa A, Boersma AJ, Liu K, Herrmann A.

Adv Mater. 2020 Jan 15:e1905309. doi: 10.1002/adma.201905309

This article is part of the Special Issue: From Responsive Materials to Interactive Materials

2019

A Trifunctional Linker for Palmitoylation and Peptide and Protein Localization in Biological Membranes.

Syga Ł, de Vries RH, van Oosterhout H, Bartelds R, Boersma AJ, Roelfes G, Poolman B.

Chembiochem. 2019 Dec 9. doi: 10.1002/cbic.201900655.

DNA Nanotechnology Enters Cell Membranes.

Huo S, Li H, Boersma AJ, Herrmann A.

Adv Sci (Weinh). 2019 Mar 20;6(10):1900043. doi: 10.1002/advs.201900043

Highlighted in Advanced Science News, April 2019.
This article is part of the Advanced Science 5th anniversary interdisciplinary article series.

Decreased Effective Macromolecular Crowding in Escherichia coli Adapted to Hyperosmotic Stress.

Liu B, Hasrat Z, Poolman B, Boersma AJ.

J Bacteriol. 2019 Apr 24;201(10). pii: e00708-18. doi: 10.1128/JB.00708-18

Selected as Article of Significant Interest (spotlight) in J. Bacteriol.

Macromolecular crowding effects on energy transfer efficiency and donor-acceptor distance of hetero-FRET sensors using time-resolved fluorescence.

Schwarz J, J Leopold H, Leighton R, Miller RC, Aplin CP, Boersma AJ, Heikal AA, Sheets ED.

Methods Appl Fluoresc. 2019 Feb 19;7(2):025002. doi: 10.1088/2050-6120/ab0242

Crowding Effects on Energy-Transfer Efficiencies of Hetero-FRET Probes As Measured Using Time-Resolved Fluorescence Anisotropy.

Leopold HJ, Leighton R, Schwarz J, Boersma AJ, Sheets ED, Heikal AA.

J Phys Chem B. 2019 Jan 17;123(2):379-393. doi: 10.1021/acs.jpcb.8b09829

2018

How Important Is Protein Diffusion in Prokaryotes?

Schavemaker PE, Boersma AJ, Poolman B.

Front Mol Biosci. 2018 Nov 13;5:93. doi: 10.3389/fmolb.2018.00093.

Special issue on biochemical reactions in cytomimetic media edited by A.P. Minton and G. Rivas

Rotational and translational diffusion of size-dependent fluorescent probes in homogeneous and heterogeneous environments.

Lee HB, Cong A, Leopold H, Currie M, Boersma AJ, Sheets ED, Heikal AA.

Phys Chem Chem Phys. 2018 Oct 7;20(37):24045-24057. doi: 10.1039/c8cp03873b

Influence of Fluorescent Protein Maturation on FRET Measurements in Living Cells.

Liu B, Mavrova SN, van den Berg J, Kristensen SK, Mantovanelli L, Veenhoff LM, Poolman B, Boersma AJ.

ACS Sens. 2018 Sep 28;3(9):1735-1742. doi: 10.1021/acssensors.8b00473

Selected in "Rising Stars in Sensing" virtual issue of ACS Sensors 2020

Genetically Encoded Förster Resonance Energy Transfer-Based Biosensors Studied on the Single-Molecule Level.

Höfig H, Otten J, Steffen V, Pohl M, Boersma AJ, Fitter J.

ACS Sens. 2018 Aug 24;3(8):1462-1470. doi: 10.1021/acssensors.8b00143

2017

Ionic Strength Sensing in Living Cells.

Liu B, Poolman B, Boersma AJ.

ACS Chem Biol. 2017 Oct 20;12(10):2510-2514. doi: 10.1021/acschembio.7b00348

Highlighted in Chemical & Engineering News, October 2017
Cover image ACS Chem. Biol. October 2017
Meet our authors highlight Boqun Liu

Fluorescence Dynamics of a FRET Probe Designed for Crowding Studies.

Currie M, Leopold H, Schwarz J, Boersma AJ, Sheets ED, Heikal AA.

J Phys Chem B. 2017 Jun 15;121(23):5688-5698. doi: 10.1021/acs.jpcb.7b01306.

Design and Properties of Genetically Encoded Probes for Sensing Macromolecular Crowding.

Liu B, Åberg C, van Eerden FJ, Marrink SJ, Poolman B, Boersma AJ.

Biophys J. 2017 May 9;112(9):1929-1939. doi: 10.1016/j.bpj.2017.04.004.

Microorganisms maintain crowding homeostasis.

van den Berg J, Boersma AJ, Poolman B.

Nat Rev Microbiol. 2017 May;15(5):309-318. doi: 10.1038/nrmicro.2017.17

2016

Semisynthetic Nanoreactor for Reversible Single-Molecule Covalent Chemistry.

Lee J, Boersma AJ, Boudreau MA, Cheley S, Daltrop O, Li J, Tamagaki H, Bayley H.

ACS Nano. 2016 Sep 27;10(9):8843-50. doi: 10.1021/acsnano.6b04663

Highlighted in Nanotechweb.org, 2016.

2015

Associative Interactions in Crowded Solutions of Biopolymers Counteract Depletion Effects.

Groen J, Foschepoth D, te Brinke E, Boersma AJ, Imamura H, Rivas G, Heus HA, Huck WT.

J Am Chem Soc. 2015 Oct 14;137(40):13041-8. doi: 10.1021/jacs.5b07898

Highlighted in Derek Lowe’s “in the pipeline” blog

Protein engineering: The power of four.

Boersma AJ, Roelfes G.

Nat Chem. 2015 Apr;7(4):277-9. doi: 10.1038/nchem.2220

A sensor for quantification of macromolecular crowding in living cells.

Boersma AJ, Zuhorn IS, Poolman B.

Nat Methods. 2015 Mar;12(3):227-9, 1 p following 229. doi: 10.1038/nmeth.3257

Highlighted in NWO newsletter, 2015
Highlighted in Biophysical Society newsletter (with interview), 2015
News articles in kennislink.nl, University of Groningen website, AzoSensors.com, Science Newsline, Phys.org, Technobahn, EurekAlert!, Science Daily, Bioportfolio, Nanowerk Nanotechnology News, and others.

Characterisation of the interactions between substrate, copper(II) complex and DNA and their role in rate acceleration in DNA-based asymmetric catalysis.

Draksharapu A, Boersma AJ, Browne WR, Roelfes G.

Dalton Trans. 2015 Feb 28;44(8):3656-63. doi: 10.1039/c4dt02734e.

Binding of copper(II) polypyridyl complexes to DNA and consequences for DNA-based asymmetric catalysis.

Draksharapu A, Boersma AJ, Leising M, Meetsma A, Browne WR, Roelfes G.

Dalton Trans. 2015 Feb 28;44(8):3647-55. doi: 10.1039/c4dt02733g.

EARLIER

Continuous stochastic detection of amino acid enantiomers with a protein nanopore.

Boersma, A.J.; Bayley, H. Angew. Chem. Int. Ed. 2012, 51, 9606.

Real-time detection of multiple neurotransmitters with a protein nanopore.

Boersma, A.J.; Brain, K.L.; Bayley, H. ACS Nano 2012, 6, 5304.

Highlighted in Nanomedicine, 2012.

Ligand denticity controls enantiomeric preference in DNA-based asymmetric catalysis.

Boersma, A.J.; de Bruin, B.; Feringa, B.L.; Roelfes, G. Chem. Commun. 2012, 2394.

Highlighted in Chemistry & Industry, 2012.

Catalytic enantioselective syn hydration of enones in water using a DNA-based catalyst.

Boersma, A.J.; Coquière, D.; Geerdink, D.; Rosati, F.; Feringa, B.L.; Roelfes, G. Nature Chem. 2010, 2, 991.

Highlighted on the NWO website, Chemisch2Weekblad
Synfacts highlight of the month February
Selected in Faculty of 1000

On the role of DNA in DNA-based catalytic enantioselective conjugate addition reactions.

Dijk, E.W.; Boersma, A.J.; Feringa, B.L.; Roelfes, G. Org. Biomol. Chem. 2010, 8, 3868.

DNA-based asymmetric catalysis.

Boersma, A.J.; Megens, R.P.; Feringa, B.L.; Roelfes, G. Chem. Soc. Rev. 2010, 39, 2083.

A kinetic and structural investigation of DNA-based asymmetric catalysis using the first generation ligands.

Rosati, F.; Boersma, A.J.; Klijn, J.E.; Meetsma, A.; Feringa, B.L.; Roelfes, G. Chem. Eur. J. 2009, 15, 9596.

Enantioselective Friedel-Crafts reactions in water using a DNA-based catalyst.

Boersma, A.J.; Feringa, B.L.; Roelfes, G. Angew. Chem. Int. Ed. 2009, 48, 3346.

Highlighted in Synfacts 2009(7)

DNA-based asymmetric catalysis: Sequence-dependent rate acceleration and enantioselectivity.

Boersma, A.J.; Klijn, J.E.; Feringa, B.L.; Roelfes, G. J. Am. Chem. Soc. 2008, 130, 11783.

Highlighted in JACS Select #4

α,β-Unsaturated 2-acyl imidazoles as a practical class of dienophiles for the DNA-based catalytic asymmetric Diels-Alder reaction in water.

Boersma, A.J.; Feringa, B.L.; Roelfes, G. Org. Lett. 2007, 9, 3647.

Highlighted on organic-chemistry.org, august 2008

Highly enantioselective DNA-based catalysis.

Roelfes, G.; Boersma, A.J.; Feringa, B.L. Chem. Commun. 2006, 635.

Hot paper in Chemical Communications.
Highlighted in Chemistry World, march 2006
Highlighted in Nature news & views, 7 dec 2006

Metal-catalyzed cotrimerization of arynes and alkenes.

Quintana, I.; Boersma, A.J.; Peña, D.; Pérez, D.; Guitián, E. Org. Lett. 2006, 8, 3347.

Catalytic enantioselective conjugate addition of dialkylzinc reagents to N-substituted-2,3-dehydro-4-piperidones.

Sebesta, R.; Pizzuti, M.G.; Boersma, A.J.; Minnaard, A.J.; Feringa, B.L. Chem. Commun. 2005, 1711.

AVAILABLE POSITIONS

STUDENT INTERNSHIPS

Student internships: Students that would like to obtain experience in one of our research topics, please contact Arnold

RESEARCH ASSISTANT

We are looking for a research assistant with experience in biochemistry/molecular biology. More information here

NO POSITION ADVERTIZED, BUT INTERESTED?

Strong PhD and Postdoc candidates are encouraged to get in contact with Arnold.

CONTACT US

DWI Leibniz Institut für Interaktive Materialien
Forckenbeckstrasse 50
D-52056 Aachen, Germany

boersma[at]dwi.rwth-aachen.de