Renske de Veer (rdeveer)
Summary Nanomedicine
HC 1: Cell supramolecular aggregates and nanoscale structures in health and disease
Nanomedicine: medical application of nanotechnology. Nanomedicine ranges from the medical
application of nanomaterial and biological devices, to nanoelectronics biosensors, and even possible
future application of molecular nanotechnology such as biological machines.
➔ Current problems: understanding the issues related to toxicity and environmental impact of
nanoscale materials (materials whose structure is on the scale of nanometers).
There are different perspectives in nanomedicine:
- Cell biology at nanoscale
- Principles of drug delivery systems in nanomedicine
- Nanomedicine & theranostics (therapy + diagnostics)
- Nanomedicine vs. personalized medicine
Personalized medicine begins at nanoscale:
- Nanoscale = the interactions of multiple proteins/molecules that give rise to supramolecular
assembly → multitude of proteins and other molecules that make nanoscale structures: 50 –
200 nm.
Two examples of cellular multi-molecular assemblies that justify nanomedicine approaches:
- The plasma membrane nanoscale organization
o Cell membrane is the meeting place of antigens, pathogens, signalling molecules, etc.
that are outside the cell and arrive at the cell surface. All these signals need to be
decoded by the cell → plasma membrane is a busy and versatile platform. Exquisite
nanoscale organization that allows the cell to decode all kind of signals.
o Natural delivery systems: exosomes & viruses.
Plasma membrane nanoscale organization.
Cell membrane functions
- Containment: it separates the intracellular from the extracellular environment
- Meeting platform: it receives and transduces extracellular signals (ligands, pathogens, ECM)
- Compartmentalization: lipids and proteins are organized in ordered areas to increase
signalling efficiency
- Mechanosensing: membrane investigation formed or flattened depending on mechanical
stimuli.
- The membrane is fluid, but extremely organized
,Renske de Veer (rdeveer)
- Bilayer of lipids, a lot of cholesterol (insurted in lipids), proteins that swim in the membrane.
- In the intracellular part: cytoskeleton
- Pericellular part; glycan felliments
Compartmentalization model of plasma membrane is at the nanoscale. How was this model
determined? → two different ways of lipid organization
- Ordered lipid: GSL & enriched in cholesterol molecules. Ordered lipids surrounded by
disordered.
- Disordered lipid: GPL.
➔ Lipid tend to stick together with lipids with the same properties.
- Composition of the cell membrane is dynamic. It can be modulated by all types of
parameters, including temperature, pH, and cholesterol amount.
Lipids in plasma membrane
Plasma membrane proteins
- PM proteins need to be post-translationally regulated/modified to be able to reach the
plasma membrane and stay stably there.
o Lipid anchor: GPI-anchored proteins
o Acelated proteins: lipidated, small lipid tails that favour insertion in plasma
membrane
o Nitrosylated & oleoylation proteins
o Scafold based on glycocylation: outer part of the surface.
▪ Galectins that breach different glycol proteins on surface
, Renske de Veer (rdeveer)
Type of PM compartments
- Protein-protein interactions
o Can facilitate receptor homo- or hetero-oligomerization.
o Through other proteins → tetraspanins
▪ Small clusters that regulate clustering of other proteins
- Lipid composition
o Lipid rafts
o Ceramide domains
- Protein-lipid interaction
o Some proteins will be mostly surrounded by lipids that will create a shell.
o Lipid can make glue in different types of proteins
- Cytoskeletal fences
o Actin cytoskeleton
o Microtubules network
Compartmentalization = Efficiency → cell knows where to find what.
Plasma membrane in health & disease: plasma membrane nanodomains are hotspots for cellular
signalling processes.
➔ Aberrant signal transduction at the PM is often due to dysregulation of nanodomains.
DC-SIGN: highly versatile pathogen recognition receptor.
- Expressed mostly on cells of immune system: myeloid origin → DC’s and some types of
macrophages.
- Family of CLR: design better CLR-targeting strategies.
- Pathogen receptor
o Exquisite virus receptor: dengue, hepatitis C, HIV-1 virus, measles.
o Pathogen recognition receptor: bacteria, parasites, fungi
o Endogenous ligands including ICAM-2/3 and MAC-1.
- Why are pathogen recognition receptors interesting?
o Family of receptor: calcium dependent C-type lectin receptors (CRLs). → can be used
in anti-tumour clinical trials. These receptors are made for antigens & foreign things.
Instruct them to recognize cancer cells → instruct immune systems to kill cancer
cells.
▪ Understand better the relationship between receptor spatiotemporal
organization and function.
▪ Understand better the cell membrane nanoenvironment in receptor
function.
Summary Nanomedicine
HC 1: Cell supramolecular aggregates and nanoscale structures in health and disease
Nanomedicine: medical application of nanotechnology. Nanomedicine ranges from the medical
application of nanomaterial and biological devices, to nanoelectronics biosensors, and even possible
future application of molecular nanotechnology such as biological machines.
➔ Current problems: understanding the issues related to toxicity and environmental impact of
nanoscale materials (materials whose structure is on the scale of nanometers).
There are different perspectives in nanomedicine:
- Cell biology at nanoscale
- Principles of drug delivery systems in nanomedicine
- Nanomedicine & theranostics (therapy + diagnostics)
- Nanomedicine vs. personalized medicine
Personalized medicine begins at nanoscale:
- Nanoscale = the interactions of multiple proteins/molecules that give rise to supramolecular
assembly → multitude of proteins and other molecules that make nanoscale structures: 50 –
200 nm.
Two examples of cellular multi-molecular assemblies that justify nanomedicine approaches:
- The plasma membrane nanoscale organization
o Cell membrane is the meeting place of antigens, pathogens, signalling molecules, etc.
that are outside the cell and arrive at the cell surface. All these signals need to be
decoded by the cell → plasma membrane is a busy and versatile platform. Exquisite
nanoscale organization that allows the cell to decode all kind of signals.
o Natural delivery systems: exosomes & viruses.
Plasma membrane nanoscale organization.
Cell membrane functions
- Containment: it separates the intracellular from the extracellular environment
- Meeting platform: it receives and transduces extracellular signals (ligands, pathogens, ECM)
- Compartmentalization: lipids and proteins are organized in ordered areas to increase
signalling efficiency
- Mechanosensing: membrane investigation formed or flattened depending on mechanical
stimuli.
- The membrane is fluid, but extremely organized
,Renske de Veer (rdeveer)
- Bilayer of lipids, a lot of cholesterol (insurted in lipids), proteins that swim in the membrane.
- In the intracellular part: cytoskeleton
- Pericellular part; glycan felliments
Compartmentalization model of plasma membrane is at the nanoscale. How was this model
determined? → two different ways of lipid organization
- Ordered lipid: GSL & enriched in cholesterol molecules. Ordered lipids surrounded by
disordered.
- Disordered lipid: GPL.
➔ Lipid tend to stick together with lipids with the same properties.
- Composition of the cell membrane is dynamic. It can be modulated by all types of
parameters, including temperature, pH, and cholesterol amount.
Lipids in plasma membrane
Plasma membrane proteins
- PM proteins need to be post-translationally regulated/modified to be able to reach the
plasma membrane and stay stably there.
o Lipid anchor: GPI-anchored proteins
o Acelated proteins: lipidated, small lipid tails that favour insertion in plasma
membrane
o Nitrosylated & oleoylation proteins
o Scafold based on glycocylation: outer part of the surface.
▪ Galectins that breach different glycol proteins on surface
, Renske de Veer (rdeveer)
Type of PM compartments
- Protein-protein interactions
o Can facilitate receptor homo- or hetero-oligomerization.
o Through other proteins → tetraspanins
▪ Small clusters that regulate clustering of other proteins
- Lipid composition
o Lipid rafts
o Ceramide domains
- Protein-lipid interaction
o Some proteins will be mostly surrounded by lipids that will create a shell.
o Lipid can make glue in different types of proteins
- Cytoskeletal fences
o Actin cytoskeleton
o Microtubules network
Compartmentalization = Efficiency → cell knows where to find what.
Plasma membrane in health & disease: plasma membrane nanodomains are hotspots for cellular
signalling processes.
➔ Aberrant signal transduction at the PM is often due to dysregulation of nanodomains.
DC-SIGN: highly versatile pathogen recognition receptor.
- Expressed mostly on cells of immune system: myeloid origin → DC’s and some types of
macrophages.
- Family of CLR: design better CLR-targeting strategies.
- Pathogen receptor
o Exquisite virus receptor: dengue, hepatitis C, HIV-1 virus, measles.
o Pathogen recognition receptor: bacteria, parasites, fungi
o Endogenous ligands including ICAM-2/3 and MAC-1.
- Why are pathogen recognition receptors interesting?
o Family of receptor: calcium dependent C-type lectin receptors (CRLs). → can be used
in anti-tumour clinical trials. These receptors are made for antigens & foreign things.
Instruct them to recognize cancer cells → instruct immune systems to kill cancer
cells.
▪ Understand better the relationship between receptor spatiotemporal
organization and function.
▪ Understand better the cell membrane nanoenvironment in receptor
function.
