Spider silk is well known for its extreme mechanical properties, this natural fiber is tougher than any other man-made fiber. Spider silk has also been used in traditional medicine to stop bleedings and to imprive wound healing. In animal studies, silk reeled from spiders has succesfully been employed to achieve nerve regeneration of injured peripheral nerves. I study spider silk with the aim to generate a biomaterial to be used in regenerative medicine and as matrix for cell culture.
We can produce artificial spider silk by letting bacteria produce partial spider silk proteins. These proteins self-assemble into fibers that match mammalian tendons in terms of tensile strength. However, to produce more defined fibers that can be employed for medical applications, we need to learn how to control the solubility and assembly of the silk proteins. Spider silk is stored at extreme concentrations (30-50% w/w, in an aqueous solution) in the spider’s silk glands, and is transformed into a solid fiber within fractions of a second in a defined part of the spinning apparatus. Clearly, this process must be highly regulated and we have recently revealed the physiological conditions along the spider silk spinning apparatus, as well as the molecular mechanisms that controls silk fiber formation. Based on these insights we have engineered a biomimetic artificial spinning device in which we can spin hundreds of meters of artificial spider silk. The silk we produce will be tested for the treatment of diseases and injuries for which there is no or poor treatment options available due to the lack of suitable materials. Specifically, we use human pluripotent stem cells and progenitor cells in cell culture experiments were we aim at developing novel treatments for e.g. cardiac disease and spinal cord injuries. By understanding how spiders manage to regulate protein solubility and assembly, we hope to also get insights into how other proteins form aggregates that are associated with disease (e.g. Alzheimer’s disease).
Another line of research concerns the spider silk proteins’ N-terminal domain (NT). NT plays an important role in fiber formation; it mediates solubility to silk proteins at high pH and rapid fiber formation when the pH is lowered (as in the silk production apparatus). We study NT to understand the molecular mechanisms behind these traits and aim to make use of our findings for biotechnological applications. For example, in one project we employ NT to produce protein-based drugs and drug candidates since NT seems to be Nature´s way of increasing solubility of aggregation prone proteins. Many of the new drugs and drug candidates generated by the pharmaceutical industry are proteins or peptides that quite often are difficult to produce, but by using NT we hope to provide a more efficient and cheap way of production.
Our recent understanding of NT has enabled us to produce artificial lung surfactant in an efficient process at very low cost. This advancement has opened up the possibility to use lung surfactant as a drug delivery vehicle. Lung surfactant spreads very rapidly across a mucosal or serosal surface and it efficiently carries for example some antibiotics and corticosteroids with it. Since lung surfactant for the first time can be produced very cost-efficiently, we are now exploiting this invention to develop a novel drug carrier for the treatment of respiratory disease and we are also investigating if the surfactant preparations we make can be used to treat acute respiratory distress syndrome in adults.
Academic honours, awards and prizes
Selected member of the Young Academy of Sweden 2015-2020.
Medal of Merit in Silver from the Swedish University of Agricultural Sciences, 2012.
Nicholson Award from Rockefeller University in 2012. Award: 25 000 USD.
Best Paper Award 2013. Materials.
Entered the list of Swedens 33 most interesting technology-driven companies in 2012 with Spiber Technologies AB
Winner of VINN NU competition (VINNOVA) in 2008 with Spiber Technologies AB
Carbonic anhydrase generates CO2 and H+ that drive spider silk formation via opposite effects on the terminal domains
PLoS biology 2014;12(8):e1001921-
Controlled assembly: a prerequisite for the use of recombinant spider silk in regenerative medicine?
Acta biomaterialia 2014;10(4):1627-31
Evaluation of Functionalized Spider Silk Matrices: Choice of Cell Types and Controls are Important for Detecting Specific Effects
Frontiers in bioengineering and biotechnology 2014;2():50-
Recombinant spider silk genetically functionalized with affinity domains
Sequential pH-driven dimerization and stabilization of the N-terminal domain enables rapid spider silk formation
Nature communications 2014;5():3254-
Spider silk for xeno-free long-term self-renewal and differentiation of human pluripotent stem cells
Morphology and Composition of the Spider Major Ampullate Gland and Dragline Silk
Control of amyloid assembly by autoregulation
The Biochemical journal 2012;447(2):185-92
Full-Length Minor Ampullate Spidroin Gene Sequence
PLOS ONE 2012;7(12):e52293-
Invited Review Current Progress and Limitations of Spider Silk for Biomedical Applications
pH-Dependent Dimerization of Spider Silk N-Terminal Domain Requires Relocation of a Wedged Tryptophan Side Chain
JOURNAL OF MOLECULAR BIOLOGY 2012;422(4):477-87
Recombinant spider silk matrices for neural stem cell cultures
Functionalisation of recombinant spider silk with conjugated polyelectrolytes
JOURNAL OF MATERIALS CHEMISTRY 2011;21(9):2909-2915
Spider silk proteins: recent advances in recombinant production, structure-function relationships and biomedical applications
CELLULAR AND MOLECULAR LIFE SCIENCES 2011;68(2):169-84
A pH-Dependent Dimer Lock in Spider Silk Protein
JOURNAL OF MOLECULAR BIOLOGY 2010;404(2):328-36
Recombinant spider silk as matrices for cell culture
Self-assembly of spider silk proteins is controlled by a pH-sensitive relay
Tissue Response to Subcutaneously Implanted Recombinant Spider Silk: An in Vivo Study
Macroscopic fibers self-assembled from recombinant miniature spider silk proteins
Major ampullate spidroins from Euprosthenops australis: multiplicity at protein, mRNA and gene levels
INSECT MOLECULAR BIOLOGY 2007;16(5):551-61
N-terminal nonrepetitive domain common to dragline, flagelliform, and cylindriform spider silk proteins
Spider silk proteins - Mechanical property and gene sequence
ZOOLOGICAL SCIENCE 2005;22(3):273-81
The JNK interacting protein JIP-1 and insulin like growth factor II genes are co-expressed in human embryonic tumours
ANTICANCER RESEARCH 2005;25(2A):1075-8