Membrane and Subcellular

Biochemistry

Arief Wibowo
Cardiologist - Molecular Biologist
Depatment of Biochemistry, Faculty of Medicine
University Jenderal Achmad Yani
Lecture Outline

01 Fundamental Concepts of Membrane Biochemistry

02 Advanced Topics in Membrane Biochemistry

03 Subcellular Biochemistry Concepts

04 Clinical Applications

05 Emerging Research and Future Directions

06 Integration with Other Disciplines

Fundamental Concepts of Membrane
Biochemistry
 01 Fundamental Concepts of Membrane Biochemistry

Biological membrane structure

Double-sheet, bilayer (phospholipid bilayer)

key components of membrane structure

maintain the structural integrity,

Membrane organization, and flow of
material through membranes.

found in the form of

Sugar glycoprotein and glycolipid

Protein

Lipid
01 Fundamental Concepts of Membrane Biochemistry

Membrane Proteins
Function of Membrane Proteins

Transporter
Facilitate the movement of molecules and
ions

Signal transduction
Act as receptors for chemical messengers

Lipid anchored Enzymatic activity

protein
Process metabolites and substrates for
various metabolic pathways

permanently attached to the membrane,
forming channels or transporters for molecules
and ions
Cell adhesion
Connecting and joining cells together
easily removed, associated
with the membrane through Cell recognition
non-covalent and covalent Serving as markers for cellular
interactions identification
01 Fundamental Concepts of Membrane Biochemistry

Membrane Fluidity and Dynamics

fluidity of the membrane lipid bilayers depend on:

Lipid composition temperature

Lower transition temperature Higher transition temperature

https://www.sciencedirect.com/science/article/pii/S0005273604002032
01 Fundamental Concepts of Membrane Biochemistry

Membrane Transport Mechanisms

01 Fundamental Concepts of Membrane Biochemistry

Signal Transduction Across Membranes

Common signal
gradients of ions or transduction pathway:
molecules across them Protein phosphorylation

three main forms

of receptor action
- relay of signal
- application
- Integration

Produced desired
cellular response
depend on the type of
cell itself
Advanced in Membrane Biochemistry
 02 Advanced Topics in Membrane Biochemistry

Membrane Rafts and Domains

Major role of lipid raft
● Endocytosis
● Exocytosis
● Cellular signaling.

Rafts are small platforms

that can float freely in the
non-activated state but
coalesce to form larger
platforms when activated,
allowing proteins to meet
and perform functions in
signaling, processing, and
transport.

https://www.frontiersin.org/articles/10.3389/fmicb.2021.631274/full
02 Advanced Topics in Membrane Biochemistry

Regulation of
Membrane
Fusion and
Vesicle
Trafficking
 02 Advanced Topics in Membrane Biochemistry

Receptor-Mediated Endocytosis

Process of receptor-mediated endocytosis

Specific ligand bind to the receptor

trigger the formation of clathrin-coated pits or caveolae

uncoated vesicle

vesicle formed coated with clathrin or caveolar

fusion with membrane

FBAR protein has been proposed to initiate membrane curvature

and mediate endocytosis via their binding partners

https://pubmed.ncbi.nlm.nih.gov/19499185/
 02 Advanced Topics in Membrane Biochemistry

SNARE-mediated
membrane fusion

https://www.sciencedirect.com/science/article/pii/S0306452211006324
02 Advanced Topics in Membrane Biochemistry

Ion Channels and Pumps

ion channel and pump play role in various

physiological processes, including:
● flow of nerve impulses
● muscle contraction
● cell division, and hormone
secretion.

selectivity filter which allows only one

type of ion to travel across.

Ion channels can be either non-gated or

gated channel.

Signalling ion depends on electrical

gradients driven in turn by sodium (Na+)
and potassium (K+) channels. This
channel and pump helping to equilibrate
both sides of the membrane and maintain
cellular homeostasis.
Subcellular Biochemistry Concepts
03 Subcellular Biochemistry Concepts

Organelle Structure and Function

Mitochondria
Nucleus
Generate most of the chemical
Serves as the repository of
energy (ATP) needed to power
genetic information and the cell's
the cell's biochemical reactions.
control center.

Ribosome Peroxisome
Protein factories of the cell, use
RNA to synthesize proteins. Involve multiple metabolic
processes, including fatty acid
oxidation, ether lipid synthesis,
and reactive oxygen species
Golgi Apparatus (ROS) metabolism.
Modifies, sorts, and packages
proteins and lipids for transport Endoplasmic
to their destination within or reticulum
outside the cell.
smooth ER responsible for lipid
production and detoxification
Lysosome rough ER involved in protein
Help in digestion, waste production, particularly for export
removal, and the breakdown of out of the cell.
dead and damaged cells.
03 Subcellular Biochemistry Concepts

Mitochondrial Biochemistry
03 Subcellular Biochemistry Concepts

Lysosomal Function Peroxisome Function

Lysosomes contain enzymes that help They are critical mediators of cellular responses to various
digestion, remove waste, and break down dead forms of stress, including oxidative stress, hypoxia,
and damaged cells. starvation, cold exposure, and noise.

Crosstalk between
peroxisomes and
other organelles.

https://www.cell.com/trends/cell-biology/fulltext/S0962-8924%2821%2900030-1
03 Subcellular Biochemistry Concepts

Nucleus and DNA Transactions

Nucleus
allows gene expression to be
regulated by posttranscriptional
mechanisms, such as alternative
splicing

DNA
genetic information
repository and the
cell's control center

Nucleotides
03 Subcellular Biochemistry Concepts

Nucleus and DNA Transactions

Clinical Applications
04 Clinical Applications

Membrane Disorders and Diseases

Genetic mutation
Disorder membrane transport Membrane dysfunction

Liddle's syndrome Long QT syndrome muscle dystrophies

hyperkalemic periodic
cystic fibrosis heart failure
paralysis
nephrogenic diabetes sphingolipid storage
myotonia congenita
insipidus disorders

Wilson's disease cystinuria

 04 Clinical Applications

Pharmacological Targeting of
Membranes

Drug design targeted 3 membrane protein Therapeutic target:

targets for almost 50% of existing alter cellular

small-molecule drugs
signaling

enabling modulation
of protein-protein,
protein-lipid, and
protein-nucleic
acid interaction

https://www.nature.com/articles/nrd3028
 04 Clinical Applications

Diagnostic Techniques in Membrane

Biochemistry

Current modern techniques in clinical:

Biochemical & Biomimetic membrane

01 Biophysical methods
02 Model
for studying drug interactions with Biomimetic have been used in:
lipid membranes using:
- development of nanovectors for drug
● Fluorescent molecular probes delivery (coated with whole cellular
● Calcium imaging membranes) to achieve immune
● Chromatography escape, longer blood circulation time,
● Circular Dichroism
and targeting delivery
● Mass spectrometry
● Protein thermal shift analysis - To investigate membrane biophysics
affecting lipid-protein interaction.

http://dx.doi.org/10.3390/nano12091543
Emerging Research and Future Directions
05 Emerging Research and Future Directions

Advances in Membrane Biophysics Subcellular Biochemistry in Disease

Membrane Biophysics Subcellular biochemistry

understanding the efficiency and divided labor
within the cell, and understanding diseases by
elucidating the molecular mechanisms
underlying cellular dysfunction.
physical, computational, mathematical, biophysical

phase diagrams of different types of

Genetics Development
membranes Epigenetics
mutation of disease

Recent research Understanding the molecular basis of

Understanding the molecular dynamics subcellular processes can help identify potential
of membrane proteins therapeutic targets and develop novel treatments
for various diseases.
05 Emerging Research and Future Directions
Nanotechnology and Membrane
Engineering
Nanotechnology
development of novel materials and
methods for membrane modification
- disrupt model biological
membranes and living cell
membranes at nanomolar
concentrations
- advancement of membrane
lifespan,
- reducing the overall cost of
separation processes7.
Bioinformatics in Membrane and
Subcellular Biochemistry
Bioinformatics
understanding membrane and subcellular
biochemistry using computational methods for
predicting membrane protein structure
and function.
- discover interactions between
membrane proteins and other cellular
components
- analyze large-scale datasets, such as
genomic and proteomic data, to
uncover novel insights into the
molecular mechanisms underlying
membrane and subcellular processes
Integration with Other Disciplines
06 Integration with Other Disciplines

Interplay Between Membrane

Biochemistry and Genetics

Structure of membrane proteins are responsible as receptors that allow the cell to respond to external signals,
selective transport of molecules across the membrane, and others as electron transport and oxidative
phosphorylation.

Recent research

Interplay between membrane-bound interplay between membrane

Interplay between membrane and its
organelles and membraneless proteins and membrane
impact on cellular physiology
condensates protein-lipid interactions
 06 Integration with Other Disciplines

Cell Signaling and Membrane

Dynamics

Signaling pathways can changes to the expression of specific target genes. In such cases, dynamic patterns of signaling can
be correlated to other measurements of cell behavior to understand how the cell is using dynamics.

Cell migration

governed by a complex
network of signal transduction
pathways. For cells to
achieve productive
movement, these signaling
processes must be
differentially and
persistently localized to
particular regions of the
cell, yet they must also
respond in a dynamic fashion
to extracellular cues.

https://www.sciencedirect.com/science/article/abs/pii/S0955067415001052
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888523/

06 Integration with Other Disciplines

Metabolism and Membrane Function

Lipid-rich microdomains
signaling platforms and a
means of communication with
the intracellular environment

Cholesterol
regulating oxygen in cell
metabolism or providing
direct raw materials to
regulate cell function
06 Integration with Other Disciplines

Metabolism and Membrane Function

Cell metabolism

Cell metabolism segregated at multiple

levels of specialization (e.g., signal
transduction, oxidative
phosphorylation, lysosomal metabolic
activity, etc.), originating different kinds
of specific modular structures.

The interplay between membrane

biochemistry, genetics, cell signaling,
membrane dynamics, and metabolism is
complex and multifaceted. These
interactions are crucial for cells' proper
functioning and maintaining cellular
homeostasis.
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 Thank you

Arief Wibowo
Cardiologist - Molecular Biologist
Depatment of Biochemistry, Faculty of Medicine
Jenderal Achmad Yani University