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Dr Kristian Franze

Kristian Franze

University Lecturer, MRC Fellow
Fellow of St John's College Tel: +44 (0)1223 333761 Fax: +44 (0)1223 333840 E-mail: kf284 [at] cam.ac.uk
How to find us

PhD students. I will be pleased to consider enquiries from prospective PhD students. Please contact me by e-mail in the first instance.

Mechanics in nervous system development and pathology

Key aspects in the development of the central nervous system (CNS) include the formation of neuronal axons, their subsequent growth and guidance through thick layers of nervous tissue, and the folding of the brain. All these processes involve motion and must thus be driven by forces. However, while our understanding of the biochemical and molecular control of these processes is increasing rapidly, the contribution of mechanics remains poorly understood.
Cell motion is also crucially involved in CNS pathologies such as foreign body reactions, in which activated glial cells migrate towards and encapsulate implants (e.g., electrodes), and the failing regeneration of neurons after CNS (e.g., spinal cord) injuries. Repair can currently not be promoted. So far, research has - without any major breakthrough - mainly focused on chemical signals impeding and promoting neuronal (re)growth.
We are taking a different, interdisciplinary approach and investigate how cellular forces, local cell and tissue compliance and cellular mechanosensitivity contribute to CNS development and disease. Methods we are exploiting include atomic force microscopy, traction force microscopy, custom-built simple and complex compliant cell culture substrates, optical microscopy including confocal laser scanning microscopy and cell biological techniques. We have shown, for example, that nervous tissue is mechanically inhomogeneous. Furthermore, we found that neurons constantly exert forces on their environment and that both neurons and glial cells respond to mechanical cues. Understanding how and when CNS cells actively exert forces and respond to their mechanical environment will shed new light on CNS development, and it could eventually lead to novel biomedical approaches to treat or circumvent pathologies that involve mechanical signalling.

Retina optics
Retinae of all vertebrates are inverted with respect to their optical function. Before light can be detected by photoreceptor cells it passes thick layers of potentially light scattering tissue. This scattering should significantly reduce image quality. However, different vertebrate species have developed highly specialised optical structures improving light transmission. For example, we have shown that Muller glial cells may act as living optical fibers. Furthermore, the grouped retina of the elefant nose fish may enable this non-predatory fish to see twice as far as its predators. There are many more retinal specialisations throughout the anmial kingdom. Understanding their functionality might lead to the development of new optical elements with unpredicted applications.

Research team:
Sarra Achouri (postdoc)
Lars Bollmann (Masters student)
Sarah Foster (Masters student)
Helene Gautier (postdoc)
Kathrin Holtzmann (PhD student, Physics/VetSchool)
Maximilian Jakobs (Masters student)
David Koser (PhD student)
Eva Pillai (Research Assitant)
Rajesh Shahapure (postdoc)
Joy Thompson (PhD student)

Previous lab members:
Emad Moeendarbary (postdoc, now Wellcome Trust Fellow at MIT)
Sara Rolle (Masters student, now PhD student in Cambridge)
Graham Sheridan (postdoc, now Lecturer at University of Brighton)
Elke Ulbricht (postdoc, now at University of Dresden)

Main collaborators:
Christoph Ballestrem (Centre for Cell Matrix Research, University of Manchester)
Kevin Chalut (Physics and SCRI, Cambridge)
James Fawcett (Brain Repair Centre, Cambridge)
Malte Gather (Physics & Astronomy, University of St. Andrews)
Jochen Guck (Technical University Dresden, Germany)
Bill Harris (PDN, Cambridge)
Christine Holt (PDN, Cambridge)
Thora Karadottir (SCRI, Cambridge)
Andreas Reichenbach (University of Leipzig, Germany)
Benedicte Sanson (PDN, Cambridge)
Giuliano Scarcelli (Wellman Center for Photomedicine, Harward Medical School, USA)

Main sources of funding: MRC, HFSP, Leverhulme Trust, Royal Society, Wellcome Trust, Newton Trust

Publications:

Pagliara S*, Franze K*, McClain CR, Wylde G, Fisher CL, Franklin RJM, Kabla AJ, Keyser UF, Chalut KJ: Auxetic nuclei in embryonic stem cells exiting pluripotency. Nature Materials 13:638-644 (2014)

Moshayedi P, Ng G, Kwok JC, Yeo GSH, Bryant C, Fawcett J, Franze K*, Guck J: The relationship between glial cell mechanosensitivity and foreign body reactions in the central nervous system. Biomaterials 35(13):3919-3925 (2014)

Franze K: The mechanical control of nervous system development. Development 140:3069-3077 (2013)

Franze K, Janmey P, Guck J: Mechanics in Neuronal Development and Repair. Annual Reviews in Biomedical Engineering 15:227-251 (2013)

Hardie RC and Franze K: Photomechanical responses in Drosophila photoreceptors. Science 338(6104):260-263 (2012)

Kuo CHR, Xian J, Brenton JD, Franze K*, Sivaniah E*: Complex stiffness gradient substrates for studying mechanotactic cell migration. Advanced Materials 24(45):6059-6064 (2012)

Kreysing M, Pusch R, Haverkate D, Landsberger M, Engelmann J, Ruiter J, Mora-Ferrer C, Ulbricht E, Grosche J, Franze K, Streif S, Schumacher S, Makarov F, Kacza J, Guck J, Wolburg H, Bowmaker J, von der Emde G, Schuster S, Wagner HJ, Reichenbach A, Francke M: Photonic Crystal Light Collectors in Fish Retina Improve Vision in Turbid Water. Science 336(6089):1700-1703 (2012)

Verho T, Korhonen JT, Sainiemi L, Jokinen V, Bower C, Franze K, Franssila S, Andrew P, Ikkala O, Ras RHA: Reversible Switching between Superhydrophobic States on a Hierarchically Structured Surface. Proc Natl Acad Sci USA 109(26):10210-10213 (2012)

Reichenbach A, Franze K, Agte S, Junek S, Wurm A, Grosche J, Savvinov A, Guck J, Skatchkov SN: Live Cells as Optical Fibers in the Vertebrate Retina. In Selected Topics on Optical Fiber Technology. M. Yasin, S. W. Harun and H. Arof, editors. InTech. (2012)

Franze K: Atomic force microscopy and its contribution to understanding the development of the nervous system. Current Opinion in Genetics & Development 21(5):530-537 (2011)

Betz T, Koch D, Lu YB, Franze K, Käs J: Growth cones as soft and weak force generators. Proc Natl Acad Sci USA 108(33):13420-13425 (2011)

Franze K, Francke M, Guenter K, Christ AF, Koerber N, Reichenbach A and Guck J: Spatial mapping of the mechanical properties of the living retina using scanning force microscopy. Soft Matter 7(7):3147-3154 (2011)

Franze K and Guck J: The biophysics of neuronal growth. Reports on Progress in Physics 73(9):094601(19pp) (2010)

Moshayedi P, da F Costa L, Christ AF, Lacour SP, Fawcett J, Guck J and Franze K: Mechanosensitivity of astrocytes on optimized polyacrylamide gels analyzed by quantitative morphometry. Journal of Physics: Condensed Matter 22(19):194114(11pp) (2010)

Christ AF, Franze K, Gautier H, Moshayedi P, Franklin RJM, Karadottir RT, Guck J: Mechanical difference between white and gray matter in the rat cerebellum measured by scanning force microscopy. Journal of Biomechanics 43(15):2986-92 (2010)

Poetes R, Holtzmann K, Franze K, Steiner U: Metastable underwater superhydrophobicity. Physical Review Letters 105(16):166104(4pp) (2010)

Lindqvist N, Liu Q, Zajadacz J, Franze K and Reichenbach A: Retinal Glial (Muller) Cells Sense and Respond to Tissue Stretch. Investigative Ophthalmology & Visual Science 51(3):1683-90 (2010)

Franze K, Gerdelmann J, Weick M, Betz T, Pawlizak S, Lakadamyali M, Bayer J, Rillich K, Gogler M, Lu YB, Reichenbach A, Janmey P and Kas J: Neurite branch retraction is caused by a threshold-dependent mechanical impact. Biophysical Journal 97(7):1883-1890 (2009)

Franze, K, Reichenbach A, Kas J: Biomechanics of the CNS. In Mechanosensitivity in Cells and Tissues: Nervous system. A. Kamkin and I. Kiseleva, editors. Springer, New York. (2008)

Franze K, Grosche J, Skatchkov SN, Schinkinger S, Foja C, Schild D, Uckermann O, Travis K, Reichenbach A, Guck J: Muller cells are living optical fibers in the vertebrate retina. Proc Natl Acad Sci USA 104(20):8287-8292 (2007)

Ehrlicher A, Betz T, Stuhrmann B, Gogler M, Koch D, Franze K, Lu YB, Kas J: Optical Neuronal Guidance. Methods in Cell Biology 83:495-520 (2007)

Lu YB*, Franze K*, Steinhauser C, Kirchhoff F, Wolburg H, Guck J, Janmey P, Kas J, Reichenbach A: Viscoelastic properties of individual glial cells and neurons in the CNS. Proc Natl Acad Sci USA 103(47):17759-17764 (2006) (*equal contributions)

Biedermann B, Bringmann A, Franze K, Faude F, Wiedemann P, Reichenbach A: GABA(A) receptors in Muller glial cells of the human retina. Glia 46(3):302-310 (2004)

Uckermann O, Iandiev I, Francke M, Franze K, Grosche J, Wolf S, Kohen L, Wiedemann P, Reichenbach A, Bringmann A: Selective staining by vital dyes of Müller glial cells in retinal wholemounts. Glia 45(1):59-66 (2004)

Links:
Physical Biology in Cambridge
Physics of Living Matter Symposium
Cambridge Neuroscience

Calcium signal after mechanical stimulation

Above: Calcium influx into a neuron after experiencing mechanical stress.

Muller cell light guidance

Above: Muller cells serve as living optical fibers in the vertebrate retina.