Group Leader: Dr. Kristina Riehemann
We analyse properties and behaviour of living cells with nanotechnological tools. Moreover, we investigate cellular reactions at the interface of nanostructured surfaces/living systems
Inflammation is an integral part of many healing processes; a directed and well-tuned physiological aspect of the body’s recovering. It may, however, get out of control and develop into a pathologic chronic inflammation (CI), a disease by itself. What makes CI so insidious is the fact that the typical patient history is one of decade-long suffering. Most symptoms can be controlled with palliative therapy for some time - but often the price paid by the patient is a dramatically reduced quality of life (QOL) as well as potentially life-threatening side effects from the drugs used. The range of CI conditions is remarkably broad, and so is the variety of causes (e.g. non-healing acute inflammation, autoimmune reactions or a hyperactive immune system).
Furthermore, recent evidence indicates that uncontrolled CI may be a significant underlying cause of cancer, atherosclerosis, vascular and heart diseases and a number of other diseases related to systemic stress. Additionally, a direct relationship between senescence of the immune system and CI in elderly people was demonstrated. Thus, CI may be the basic cause of many of the age-related chronic diseases.
Nanoparticles (NP) and nanostructured surfaces (NaSu) are finding more and more their way to clinical applications: Microsensors are used for diagnostic purposes, magnetic NP are applied for cancer treatment and drugs coupled to NP are used to enhance the effect of medications addionally nanostructured surfaces are used for prosthetics. An example for negative side effects of this application is the activation of the secretion of inflammatory active cytokine (IL1-beta, IL-6, IL-10) An effect of NaSu could be the generation of autoimmune diseases mediated by macrophages.
Macrophages are, among others, part of the unspecific cellular and humoral immune response as well as of the specific reaction of the immune system. These cells become phagocytosing foreign material by binding C3BC5B and instruct lymphocytes to generate antibodies against the phagocytosed material. These antibodies recognise adsorbed material on NP, inducing auto-immunity. An example is wear debris generated by orthopaedic implants. Patients with such implants exhibit a statistically significant increase in the incidence of auto-immune diseases. Next to the effect of NP and NaSu on the immune system the effect of NP on the biological barriers are investigated. Measure for the intactness of such layers is the “Transepithelial Electrical Resistance (TER)” In cooperation with nanoAnalytics GmbH the cellZscope™, a device for the high throughput investigation of the TER, was optimized for different applications.
After stimulation leukocytes show a dramatic increase in the activity of its membrane, manifested by the appearance of dynamic membrane structures such as lamellipodia, filopodia, and membrane ruffles.
The external stimulus turns on membrane bound activators, like Cdc42 and PIP2, which cause increased branching and polymerization of the actin cytoskeleton in their vicinity leading to a local protrusive force on the membrane. Circulating leukocytes captured by the endothelium experience in seconds an order of magnitude increase in Fluid Shear Stress (FSS). This stimulus enhances properties like motility, directs migration, enhances transmigration of activated lymphocytes, and alters phagocytosis. Thus, the FSS response of human leukocytes is an important regulator of the immune response. Further investigations on the physical properties of different types of leukocytes will be performed to demonstrate the role of a change in physical condition of the environment of cells. Physical properties of macrophages are investigated under normal conditions and after inflammatory activation.